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Is benzophenone safe in skin care? Part 1: Risks to humans
Benzophenones are a family of compounds that include dixoxybenzone, sulisobenzone, and benzophenone-3, or oxybenzone. These . Benzophenones (BPs) act as penetration enhancers, as they modify the structure of the skin and facilitate the absorption of other chemical ingredients into the body. The best known uses of these compounds are as perfume fixatives and sunscreen agents.
Sunscreens and benzophenones
BP-2, -3 and -4 are used as sunscreens but have many downsides. They are well known photoallergens, are toxic to aquatic animals (especially BP-3), and are found in urine. BP-2 has weak estrogenic effects, and some studies suggest that it decreases fertility in men. BP-4 can increase absorption of pesticides. BP-3 is banned in Hawaii because of the risk to coral and is the most worrisome.
In particular, BP-3 is known to protect skin and hair from UV radiation-induced harm.1 Unfortunately, BPs are also associated with photocontact allergies, hypersensitivity, hives, contact urticaria, anaphylaxis, hormone disruption, and DNA damage.2,3 BP-3 has also been implicated as an environmental contaminant. This column will focus on recent studies pertaining to effects on humans, primarily, and on the role of BPs in sunscreen agents.
Effects of BPs in animals
A recent study on the cytotoxicity of BP-3 against thymocytes in rats revealed that cell mortality increased significantly after 3 hours of exposure to 300 μM BP-3, but the membrane potential of thymocytes was unchanged by BP-3 exposure. In a concentration-dependent fashion, intracellular Zn2+ levels increased significantly after administration of at least 30 μM BP-3. The investigators concluded that the cytotoxicity engendered by BP-3 could be the result of oxidative stress linked to elevated intracellular Zn2+ levels.1
Effects of BPs in humans and systemic absorption
In multiple studies, exposure to BP-3, as well as to octinoxate, has been linked to endocrine and hormonal disruptions in humans and animals.4,5 Motivated by several notable observations (global increase in the use of sunscreens with UV filters; rapid rise in malignant melanoma, against which sunscreens should protect; increase in reported experimental findings of UV filters acting as endocrine disruptors), Krause et al. in 2012 reviewed animal and human data on the UV filters BP-3, 3-benzylidene camphor (3-BC), 3-(4-methyl-benzylidene) camphor (4-MBC), 2-ethylhexyl 4-methoxy cinnamate (OMC), homosalate (HMS), 2-ethylhexyl 4-dimethylaminobenzoate, and 4-aminobenzoic acid (PABA). Importantly, BP-3 was present in 96% of human urine samples in the United States, and various filters were found in 85% of the human breast milk samples in Switzerland.6
A 2019 analysis by Wang and Ganley reported that systemic absorption of the active sunscreen ingredient BP-3 can be substantial, justifying the assessment and understanding of systemic exposure to characterize the risks of long-term usage.7
Between January and February 2019, Matta et al. conducted a randomized clinical trial with 48 healthy participants to evaluate the systemic absorption and pharmacokinetics of six active ingredients in four sunscreen formulations, including avobenzone and BP-3. The researchers found that all ingredients were systemically absorbed, with plasma concentrations exceeding the Food and Drug Administration threshold for considering the waiving of further safety studies. They concluded that these results did not warrant discontinuing the use of the tested sunscreen ingredients.8 Yeager and Lim add that, while BP-3 has been incorporated into sunscreen formulations for sale in the United States since 1978, there have been no reports of adverse systemic reactions in human beings.3
However, topical reactions have elicited a different assessment. That is, in 2014, the American Contact Dermatitis Society labeled BPs the Contact Allergen of the Year, as they were identified as the most common source of photoallergic and contact allergic reactions of all UV filters.3,9
Risks of BPs in sunscreens and other skincare products
In 2015, Amar et al. investigated the photogenotoxicity and apoptotic effects in human keratinocytes (HaCaT cells) of BP-1, which is used as a UV blocker in sunscreens. They found that BP-1, when exposed to UV radiation, photosensitized cells and yielded intracellular reactive oxygen species. Significant reductions in cell viability were also seen with exposure to sunlight, UVA, and UVB. The researchers also confirmed genotoxic activity, with BP-1 augmenting lipid peroxidation and upregulating apoptotic proteins. They concluded that sunscreen users should be advised to avoid products that contain BP-1.10
In 2019, Amar et al. evaluated the effects of BPs on the differential expression of proteins in HaCaT cells exposed to UVA. Their findings indicated the expression of novel proteins that helped to initiate or promote apoptosis. They concluded that, because of the predilection to render such effects in human skin keratinocytes, consumers should avoid the use of sunscreens that contain BPs as UV blocking ingredients.11
Still widely used as an effective filter against UVA2 and UVB, BP-3 was believed to be present in two thirds of nonmineral sunscreens in the United States in 2018.3,12
Notably, BP-1 and BP-3 were found in small proportions (3.7% and 4.9%, respectively) among a total of 283 products culled from various stores in Lecce, Italy, in a survey of the potentially dangerous chemicals found in rinse-off, leave-on, and makeup products in 2019.13 The authors added that the International Agency for Research on Cancer, in 2010, classified BP as potentially carcinogenic to humans (2B group).13,14
Promising use of nanocapsules
The widespread concern about the phototoxicity of BP has prompted some interesting research into workarounds. Specifically, in 2019, Barbosa et al. reported on the creation of a new sunscreen formulation using polymeric nanocapsules loading BP-3. The nanocapsules are made of poly(ε-caprolactone) carrot oil and Pluronic F68 (nonionic surfactant used in suspension cultures), and the BP-3–loaded capsules were found to be noncytotoxic in L929 fibroblast cell lines with a sun protection factor of 8.64. The researchers concluded that this promising nanocapsule may be an effective and safe way to use lipophilic sunscreen ingredients such as BP-3.15
Conclusion
The body of evidence is weighted against the use of BPs. Luckily, we have safe sunscreen choices that allow us to protect our skin without using these compounds.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Utsunomiya H et al. Chem Biol Interact. 2019 Jan 25;298:52-6.
2. Schneider SL and Lim HW. J Am Acad Dermatol. 2019 Jan;80(1):266-71.
3. Yeager DG and Lim HW. Dermatol Clin. 2019 Apr;37(2):149-57.
4. Ramos S et al. Sci Total Environ. 2015 Sep 1;526:278-311.
5. Siller A et al. Plast Surg Nur. 2019 Oct/Dec;39(4):157-60.
6. Krause M et al. Int J Androl. 2012 Jun;35(3):424-36.
7. Wang J and Ganley CJ. Clin Pharmacol Ther. 2019 Jan;105(1):161-7.
8. Matta MK et al. JAMA. 2020 Jan 21;323(3):256-67.
9. Warshaw EM et al. Dermatitis. 2013 Jul-Aug;24(4):176-82.
10. Amar SK et al. Toxicol Lett. 2015 Dec 15;239(3):182-93.
11. Amar SK et al. Toxicol Ind Health. 2019 Jul;35(7):457-65.
12. EWG. The trouble with ingredients in sunscreens. Accessed on 4 April 2020.
13. Panico A et al. J Prev Med Hyg. 2019 Mar 29;60(1):E50-7.
14. International Agency for Research on Cancer (IARC). Benzophenone. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. WHO, IARC Press, Lyon, France. 2010;101:285-304.
15. Barbosa TC et al. Toxics. 2019 Sep 22;7(4):51.
Benzophenones are a family of compounds that include dixoxybenzone, sulisobenzone, and benzophenone-3, or oxybenzone. These . Benzophenones (BPs) act as penetration enhancers, as they modify the structure of the skin and facilitate the absorption of other chemical ingredients into the body. The best known uses of these compounds are as perfume fixatives and sunscreen agents.
Sunscreens and benzophenones
BP-2, -3 and -4 are used as sunscreens but have many downsides. They are well known photoallergens, are toxic to aquatic animals (especially BP-3), and are found in urine. BP-2 has weak estrogenic effects, and some studies suggest that it decreases fertility in men. BP-4 can increase absorption of pesticides. BP-3 is banned in Hawaii because of the risk to coral and is the most worrisome.
In particular, BP-3 is known to protect skin and hair from UV radiation-induced harm.1 Unfortunately, BPs are also associated with photocontact allergies, hypersensitivity, hives, contact urticaria, anaphylaxis, hormone disruption, and DNA damage.2,3 BP-3 has also been implicated as an environmental contaminant. This column will focus on recent studies pertaining to effects on humans, primarily, and on the role of BPs in sunscreen agents.
Effects of BPs in animals
A recent study on the cytotoxicity of BP-3 against thymocytes in rats revealed that cell mortality increased significantly after 3 hours of exposure to 300 μM BP-3, but the membrane potential of thymocytes was unchanged by BP-3 exposure. In a concentration-dependent fashion, intracellular Zn2+ levels increased significantly after administration of at least 30 μM BP-3. The investigators concluded that the cytotoxicity engendered by BP-3 could be the result of oxidative stress linked to elevated intracellular Zn2+ levels.1
Effects of BPs in humans and systemic absorption
In multiple studies, exposure to BP-3, as well as to octinoxate, has been linked to endocrine and hormonal disruptions in humans and animals.4,5 Motivated by several notable observations (global increase in the use of sunscreens with UV filters; rapid rise in malignant melanoma, against which sunscreens should protect; increase in reported experimental findings of UV filters acting as endocrine disruptors), Krause et al. in 2012 reviewed animal and human data on the UV filters BP-3, 3-benzylidene camphor (3-BC), 3-(4-methyl-benzylidene) camphor (4-MBC), 2-ethylhexyl 4-methoxy cinnamate (OMC), homosalate (HMS), 2-ethylhexyl 4-dimethylaminobenzoate, and 4-aminobenzoic acid (PABA). Importantly, BP-3 was present in 96% of human urine samples in the United States, and various filters were found in 85% of the human breast milk samples in Switzerland.6
A 2019 analysis by Wang and Ganley reported that systemic absorption of the active sunscreen ingredient BP-3 can be substantial, justifying the assessment and understanding of systemic exposure to characterize the risks of long-term usage.7
Between January and February 2019, Matta et al. conducted a randomized clinical trial with 48 healthy participants to evaluate the systemic absorption and pharmacokinetics of six active ingredients in four sunscreen formulations, including avobenzone and BP-3. The researchers found that all ingredients were systemically absorbed, with plasma concentrations exceeding the Food and Drug Administration threshold for considering the waiving of further safety studies. They concluded that these results did not warrant discontinuing the use of the tested sunscreen ingredients.8 Yeager and Lim add that, while BP-3 has been incorporated into sunscreen formulations for sale in the United States since 1978, there have been no reports of adverse systemic reactions in human beings.3
However, topical reactions have elicited a different assessment. That is, in 2014, the American Contact Dermatitis Society labeled BPs the Contact Allergen of the Year, as they were identified as the most common source of photoallergic and contact allergic reactions of all UV filters.3,9
Risks of BPs in sunscreens and other skincare products
In 2015, Amar et al. investigated the photogenotoxicity and apoptotic effects in human keratinocytes (HaCaT cells) of BP-1, which is used as a UV blocker in sunscreens. They found that BP-1, when exposed to UV radiation, photosensitized cells and yielded intracellular reactive oxygen species. Significant reductions in cell viability were also seen with exposure to sunlight, UVA, and UVB. The researchers also confirmed genotoxic activity, with BP-1 augmenting lipid peroxidation and upregulating apoptotic proteins. They concluded that sunscreen users should be advised to avoid products that contain BP-1.10
In 2019, Amar et al. evaluated the effects of BPs on the differential expression of proteins in HaCaT cells exposed to UVA. Their findings indicated the expression of novel proteins that helped to initiate or promote apoptosis. They concluded that, because of the predilection to render such effects in human skin keratinocytes, consumers should avoid the use of sunscreens that contain BPs as UV blocking ingredients.11
Still widely used as an effective filter against UVA2 and UVB, BP-3 was believed to be present in two thirds of nonmineral sunscreens in the United States in 2018.3,12
Notably, BP-1 and BP-3 were found in small proportions (3.7% and 4.9%, respectively) among a total of 283 products culled from various stores in Lecce, Italy, in a survey of the potentially dangerous chemicals found in rinse-off, leave-on, and makeup products in 2019.13 The authors added that the International Agency for Research on Cancer, in 2010, classified BP as potentially carcinogenic to humans (2B group).13,14
Promising use of nanocapsules
The widespread concern about the phototoxicity of BP has prompted some interesting research into workarounds. Specifically, in 2019, Barbosa et al. reported on the creation of a new sunscreen formulation using polymeric nanocapsules loading BP-3. The nanocapsules are made of poly(ε-caprolactone) carrot oil and Pluronic F68 (nonionic surfactant used in suspension cultures), and the BP-3–loaded capsules were found to be noncytotoxic in L929 fibroblast cell lines with a sun protection factor of 8.64. The researchers concluded that this promising nanocapsule may be an effective and safe way to use lipophilic sunscreen ingredients such as BP-3.15
Conclusion
The body of evidence is weighted against the use of BPs. Luckily, we have safe sunscreen choices that allow us to protect our skin without using these compounds.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Utsunomiya H et al. Chem Biol Interact. 2019 Jan 25;298:52-6.
2. Schneider SL and Lim HW. J Am Acad Dermatol. 2019 Jan;80(1):266-71.
3. Yeager DG and Lim HW. Dermatol Clin. 2019 Apr;37(2):149-57.
4. Ramos S et al. Sci Total Environ. 2015 Sep 1;526:278-311.
5. Siller A et al. Plast Surg Nur. 2019 Oct/Dec;39(4):157-60.
6. Krause M et al. Int J Androl. 2012 Jun;35(3):424-36.
7. Wang J and Ganley CJ. Clin Pharmacol Ther. 2019 Jan;105(1):161-7.
8. Matta MK et al. JAMA. 2020 Jan 21;323(3):256-67.
9. Warshaw EM et al. Dermatitis. 2013 Jul-Aug;24(4):176-82.
10. Amar SK et al. Toxicol Lett. 2015 Dec 15;239(3):182-93.
11. Amar SK et al. Toxicol Ind Health. 2019 Jul;35(7):457-65.
12. EWG. The trouble with ingredients in sunscreens. Accessed on 4 April 2020.
13. Panico A et al. J Prev Med Hyg. 2019 Mar 29;60(1):E50-7.
14. International Agency for Research on Cancer (IARC). Benzophenone. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. WHO, IARC Press, Lyon, France. 2010;101:285-304.
15. Barbosa TC et al. Toxics. 2019 Sep 22;7(4):51.
Benzophenones are a family of compounds that include dixoxybenzone, sulisobenzone, and benzophenone-3, or oxybenzone. These . Benzophenones (BPs) act as penetration enhancers, as they modify the structure of the skin and facilitate the absorption of other chemical ingredients into the body. The best known uses of these compounds are as perfume fixatives and sunscreen agents.
Sunscreens and benzophenones
BP-2, -3 and -4 are used as sunscreens but have many downsides. They are well known photoallergens, are toxic to aquatic animals (especially BP-3), and are found in urine. BP-2 has weak estrogenic effects, and some studies suggest that it decreases fertility in men. BP-4 can increase absorption of pesticides. BP-3 is banned in Hawaii because of the risk to coral and is the most worrisome.
In particular, BP-3 is known to protect skin and hair from UV radiation-induced harm.1 Unfortunately, BPs are also associated with photocontact allergies, hypersensitivity, hives, contact urticaria, anaphylaxis, hormone disruption, and DNA damage.2,3 BP-3 has also been implicated as an environmental contaminant. This column will focus on recent studies pertaining to effects on humans, primarily, and on the role of BPs in sunscreen agents.
Effects of BPs in animals
A recent study on the cytotoxicity of BP-3 against thymocytes in rats revealed that cell mortality increased significantly after 3 hours of exposure to 300 μM BP-3, but the membrane potential of thymocytes was unchanged by BP-3 exposure. In a concentration-dependent fashion, intracellular Zn2+ levels increased significantly after administration of at least 30 μM BP-3. The investigators concluded that the cytotoxicity engendered by BP-3 could be the result of oxidative stress linked to elevated intracellular Zn2+ levels.1
Effects of BPs in humans and systemic absorption
In multiple studies, exposure to BP-3, as well as to octinoxate, has been linked to endocrine and hormonal disruptions in humans and animals.4,5 Motivated by several notable observations (global increase in the use of sunscreens with UV filters; rapid rise in malignant melanoma, against which sunscreens should protect; increase in reported experimental findings of UV filters acting as endocrine disruptors), Krause et al. in 2012 reviewed animal and human data on the UV filters BP-3, 3-benzylidene camphor (3-BC), 3-(4-methyl-benzylidene) camphor (4-MBC), 2-ethylhexyl 4-methoxy cinnamate (OMC), homosalate (HMS), 2-ethylhexyl 4-dimethylaminobenzoate, and 4-aminobenzoic acid (PABA). Importantly, BP-3 was present in 96% of human urine samples in the United States, and various filters were found in 85% of the human breast milk samples in Switzerland.6
A 2019 analysis by Wang and Ganley reported that systemic absorption of the active sunscreen ingredient BP-3 can be substantial, justifying the assessment and understanding of systemic exposure to characterize the risks of long-term usage.7
Between January and February 2019, Matta et al. conducted a randomized clinical trial with 48 healthy participants to evaluate the systemic absorption and pharmacokinetics of six active ingredients in four sunscreen formulations, including avobenzone and BP-3. The researchers found that all ingredients were systemically absorbed, with plasma concentrations exceeding the Food and Drug Administration threshold for considering the waiving of further safety studies. They concluded that these results did not warrant discontinuing the use of the tested sunscreen ingredients.8 Yeager and Lim add that, while BP-3 has been incorporated into sunscreen formulations for sale in the United States since 1978, there have been no reports of adverse systemic reactions in human beings.3
However, topical reactions have elicited a different assessment. That is, in 2014, the American Contact Dermatitis Society labeled BPs the Contact Allergen of the Year, as they were identified as the most common source of photoallergic and contact allergic reactions of all UV filters.3,9
Risks of BPs in sunscreens and other skincare products
In 2015, Amar et al. investigated the photogenotoxicity and apoptotic effects in human keratinocytes (HaCaT cells) of BP-1, which is used as a UV blocker in sunscreens. They found that BP-1, when exposed to UV radiation, photosensitized cells and yielded intracellular reactive oxygen species. Significant reductions in cell viability were also seen with exposure to sunlight, UVA, and UVB. The researchers also confirmed genotoxic activity, with BP-1 augmenting lipid peroxidation and upregulating apoptotic proteins. They concluded that sunscreen users should be advised to avoid products that contain BP-1.10
In 2019, Amar et al. evaluated the effects of BPs on the differential expression of proteins in HaCaT cells exposed to UVA. Their findings indicated the expression of novel proteins that helped to initiate or promote apoptosis. They concluded that, because of the predilection to render such effects in human skin keratinocytes, consumers should avoid the use of sunscreens that contain BPs as UV blocking ingredients.11
Still widely used as an effective filter against UVA2 and UVB, BP-3 was believed to be present in two thirds of nonmineral sunscreens in the United States in 2018.3,12
Notably, BP-1 and BP-3 were found in small proportions (3.7% and 4.9%, respectively) among a total of 283 products culled from various stores in Lecce, Italy, in a survey of the potentially dangerous chemicals found in rinse-off, leave-on, and makeup products in 2019.13 The authors added that the International Agency for Research on Cancer, in 2010, classified BP as potentially carcinogenic to humans (2B group).13,14
Promising use of nanocapsules
The widespread concern about the phototoxicity of BP has prompted some interesting research into workarounds. Specifically, in 2019, Barbosa et al. reported on the creation of a new sunscreen formulation using polymeric nanocapsules loading BP-3. The nanocapsules are made of poly(ε-caprolactone) carrot oil and Pluronic F68 (nonionic surfactant used in suspension cultures), and the BP-3–loaded capsules were found to be noncytotoxic in L929 fibroblast cell lines with a sun protection factor of 8.64. The researchers concluded that this promising nanocapsule may be an effective and safe way to use lipophilic sunscreen ingredients such as BP-3.15
Conclusion
The body of evidence is weighted against the use of BPs. Luckily, we have safe sunscreen choices that allow us to protect our skin without using these compounds.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Utsunomiya H et al. Chem Biol Interact. 2019 Jan 25;298:52-6.
2. Schneider SL and Lim HW. J Am Acad Dermatol. 2019 Jan;80(1):266-71.
3. Yeager DG and Lim HW. Dermatol Clin. 2019 Apr;37(2):149-57.
4. Ramos S et al. Sci Total Environ. 2015 Sep 1;526:278-311.
5. Siller A et al. Plast Surg Nur. 2019 Oct/Dec;39(4):157-60.
6. Krause M et al. Int J Androl. 2012 Jun;35(3):424-36.
7. Wang J and Ganley CJ. Clin Pharmacol Ther. 2019 Jan;105(1):161-7.
8. Matta MK et al. JAMA. 2020 Jan 21;323(3):256-67.
9. Warshaw EM et al. Dermatitis. 2013 Jul-Aug;24(4):176-82.
10. Amar SK et al. Toxicol Lett. 2015 Dec 15;239(3):182-93.
11. Amar SK et al. Toxicol Ind Health. 2019 Jul;35(7):457-65.
12. EWG. The trouble with ingredients in sunscreens. Accessed on 4 April 2020.
13. Panico A et al. J Prev Med Hyg. 2019 Mar 29;60(1):E50-7.
14. International Agency for Research on Cancer (IARC). Benzophenone. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. WHO, IARC Press, Lyon, France. 2010;101:285-304.
15. Barbosa TC et al. Toxics. 2019 Sep 22;7(4):51.
Lost keys, missed appointments: The struggle of treating executive dysfunction
Maybe you know some of these patients: They may come late or not show up at all. They may have little to say and minimize their difficulties, often because they are ashamed of how much effort it takes to meet ordinary obligations. They may struggle to complete assignments, fail classes, or lose jobs. And being in the right place at the right time can feel monumental to them: They forget appointments, double book themselves, or sometimes sleep through important events.
It’s not just appointments. They lose their keys and valuables, forget to pay bills, and may not answer calls, texts, or emails. Their voicemail may be full and people are often frustrated with them. These are all characteristics of executive dysfunction, which together can make the routine responsibilities of life very difficult.
Treatments include stimulants, and because of their potential for abuse, these medications are more strictly regulated when it comes to prescribing. The FDA does not allow them to be phoned into a pharmacy or refills to be added to prescriptions. Patients must wait until right before they are due to run out to get the next prescription, and this can present a problem if the patient travels or takes long vacations.
And although it is not the patient’s fault that stimulants can’t be ordered with refills, this adds to the burden of treating patients who take them. It’s hard to imagine that these restrictions on stimulants and opiates (but not on benzodiazepines) do much to deter abuse or diversion.
I trained at a time when ADD and ADHD were disorders of childhood, and as an adult psychiatrist, I was not exposed to patients on these medications. Occasionally, a stimulant was prescribed in a low dose to help activate a very depressed patient, but it was thought that children outgrow issues of attention and focus, and I have never felt fully confident in the more nuanced use of these medications with adults. Most of the patients I now treat with ADD have come to me on stable doses of the medications or at least with a history that directs care.
With others, the tip-off to look for the disorder is their disorganization in the absence of a substance use or active mood disorder. Medications help, sometimes remarkably, yet patients still struggle with organization and planning, and sometimes I find myself frustrated when patients forget their appointments or the issues around prescribing stimulants become time-consuming.
David W. Goodman, MD, director of the Adult Attention Deficit Center of Maryland, Lutherville, currently treats hundreds of patients with ADD and has written and spoken extensively about treating this disorder in adults.
“There are three things that make it difficult to manage patients with ADD,” Dr. Goodman noted, referring specifically to administrative issues. “You can’t write for refills, but with e-prescribing you can write a sequence of prescriptions with ‘fill-after’ dates. Or some patients are able to get a 90-day supply from mail-order pharmacies. Still, it’s a hassle if the patient moves around, as college students often do, and there are inventory shortages when some pharmacies can’t get the medications.”
“The second issue,” he adds, “is that it’s the nature of this disorder that patients struggle with organizational issues. Yelling at someone with ADD to pay attention is like yelling at a blind person not to run into furniture when they are in a new room. They go through life with people being impatient that they can’t do the things an ordinary person can do easily.”
Finally, Dr. Goodman noted that the clinicians who treat patients with ADD may have counter-transference issues.
“You have to understand that this is a disability and be sympathetic to it. They often have comorbid disorders, including personality disorders, and this can all bleed over to cause frustrations in their care. Psychiatrists who treat patients with ADD need to know they can deal with them compassionately.”
“I am occasionally contacted by patients who already have an ADHD diagnosis and are on stimulants, and who seem like they just want to get their prescriptions filled and aren’t interested in working on their issues,” says Douglas Beech, MD, a psychiatrist in private practice in Worthington, Ohio. “The doctor in this situation can feel like they are functioning as a sort of drug dealer. There are logistical matters that are structurally inherent in trying to assist these patients, from both a regulatory perspective and from a functional perspective. Dr. Beech feels that it’s helpful to acknowledge these issues when seeing patients with ADHD, so that he is prepared when problems do arise.
“It can almost feel cruel to charge a patient for a “no-show,” when difficulty keeping appointments may be a symptom of their illness, Dr. Beech adds. But he does believe it’s important to apply any fee policy equitably to all patients. “I don’t apply the ‘missed appointment’ policy differently to a person with an ADHD diagnosis versus any other diagnosis.” Though for their first missed appointment, he does give patients a “mulligan.”
“I don’t charge, but it puts both patient and doctor on notice,” he says.
And when his patients do miss an appointment, he offers to send a reminder for the next time, which is he says is effective. “With electronic messaging, this is a quick and easy way to prevent missed appointments and the complications that arise with prescriptions and rescheduling,” says Dr. Beech.
Dr. Goodman speaks about manging a large caseload of patients, many of whom have organizational issues.
“I have a full-time office manager who handles a lot of the logistics of scheduling and prescribing. Patients are sent multiple reminders, and I charge a nominal administrative fee if prescriptions need to be sent outside of appointments. This is not to make money, but to encourage patients to consider the administrative time.”
“I charge for appointments that are not canceled 48 hours in advance, and for patients who have missed appointments, a credit card is kept on file,” he says.
In a practice similar to Dr. Beech, Dr. Goodman notes that he shows some flexibility for new patients when they miss an appointment the first time. “By the second time, they know this is the policy. Having ADHD can be financially costly.”
He notes that about 10% of his patients, roughly one a day, cancel late or don’t show up for scheduled appointments: “We keep a waitlist, and if someone cancels before the appointment, we can often fill the time with another patient in need on our waitlist.”
Dr. Goodman noted repeatedly that the clinician needs to be able to empathize with the patient’s condition and how they suffer. “This is not something people choose to have. The trap is that people think that if you’re successful you can’t have ADHD, and that’s not true. Often people with this condition work harder, are brighter, and find ways to compensate.”
If a practice is set up to accommodate the needs of patients with attention and organizational issues, treating them can be very gratifying. In settings without administrative support, the psychiatrist needs to stay cognizant of this invisible disability and the frustration that may come with this disorder, not just for the patient, but also for the family, friends, and employers, and even for the psychiatrist.
Dr. Dinah Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, Baltimore. Dr. Miller has no conflicts of interest.
A version of this article first appeared on Medscape.com.
Maybe you know some of these patients: They may come late or not show up at all. They may have little to say and minimize their difficulties, often because they are ashamed of how much effort it takes to meet ordinary obligations. They may struggle to complete assignments, fail classes, or lose jobs. And being in the right place at the right time can feel monumental to them: They forget appointments, double book themselves, or sometimes sleep through important events.
It’s not just appointments. They lose their keys and valuables, forget to pay bills, and may not answer calls, texts, or emails. Their voicemail may be full and people are often frustrated with them. These are all characteristics of executive dysfunction, which together can make the routine responsibilities of life very difficult.
Treatments include stimulants, and because of their potential for abuse, these medications are more strictly regulated when it comes to prescribing. The FDA does not allow them to be phoned into a pharmacy or refills to be added to prescriptions. Patients must wait until right before they are due to run out to get the next prescription, and this can present a problem if the patient travels or takes long vacations.
And although it is not the patient’s fault that stimulants can’t be ordered with refills, this adds to the burden of treating patients who take them. It’s hard to imagine that these restrictions on stimulants and opiates (but not on benzodiazepines) do much to deter abuse or diversion.
I trained at a time when ADD and ADHD were disorders of childhood, and as an adult psychiatrist, I was not exposed to patients on these medications. Occasionally, a stimulant was prescribed in a low dose to help activate a very depressed patient, but it was thought that children outgrow issues of attention and focus, and I have never felt fully confident in the more nuanced use of these medications with adults. Most of the patients I now treat with ADD have come to me on stable doses of the medications or at least with a history that directs care.
With others, the tip-off to look for the disorder is their disorganization in the absence of a substance use or active mood disorder. Medications help, sometimes remarkably, yet patients still struggle with organization and planning, and sometimes I find myself frustrated when patients forget their appointments or the issues around prescribing stimulants become time-consuming.
David W. Goodman, MD, director of the Adult Attention Deficit Center of Maryland, Lutherville, currently treats hundreds of patients with ADD and has written and spoken extensively about treating this disorder in adults.
“There are three things that make it difficult to manage patients with ADD,” Dr. Goodman noted, referring specifically to administrative issues. “You can’t write for refills, but with e-prescribing you can write a sequence of prescriptions with ‘fill-after’ dates. Or some patients are able to get a 90-day supply from mail-order pharmacies. Still, it’s a hassle if the patient moves around, as college students often do, and there are inventory shortages when some pharmacies can’t get the medications.”
“The second issue,” he adds, “is that it’s the nature of this disorder that patients struggle with organizational issues. Yelling at someone with ADD to pay attention is like yelling at a blind person not to run into furniture when they are in a new room. They go through life with people being impatient that they can’t do the things an ordinary person can do easily.”
Finally, Dr. Goodman noted that the clinicians who treat patients with ADD may have counter-transference issues.
“You have to understand that this is a disability and be sympathetic to it. They often have comorbid disorders, including personality disorders, and this can all bleed over to cause frustrations in their care. Psychiatrists who treat patients with ADD need to know they can deal with them compassionately.”
“I am occasionally contacted by patients who already have an ADHD diagnosis and are on stimulants, and who seem like they just want to get their prescriptions filled and aren’t interested in working on their issues,” says Douglas Beech, MD, a psychiatrist in private practice in Worthington, Ohio. “The doctor in this situation can feel like they are functioning as a sort of drug dealer. There are logistical matters that are structurally inherent in trying to assist these patients, from both a regulatory perspective and from a functional perspective. Dr. Beech feels that it’s helpful to acknowledge these issues when seeing patients with ADHD, so that he is prepared when problems do arise.
“It can almost feel cruel to charge a patient for a “no-show,” when difficulty keeping appointments may be a symptom of their illness, Dr. Beech adds. But he does believe it’s important to apply any fee policy equitably to all patients. “I don’t apply the ‘missed appointment’ policy differently to a person with an ADHD diagnosis versus any other diagnosis.” Though for their first missed appointment, he does give patients a “mulligan.”
“I don’t charge, but it puts both patient and doctor on notice,” he says.
And when his patients do miss an appointment, he offers to send a reminder for the next time, which is he says is effective. “With electronic messaging, this is a quick and easy way to prevent missed appointments and the complications that arise with prescriptions and rescheduling,” says Dr. Beech.
Dr. Goodman speaks about manging a large caseload of patients, many of whom have organizational issues.
“I have a full-time office manager who handles a lot of the logistics of scheduling and prescribing. Patients are sent multiple reminders, and I charge a nominal administrative fee if prescriptions need to be sent outside of appointments. This is not to make money, but to encourage patients to consider the administrative time.”
“I charge for appointments that are not canceled 48 hours in advance, and for patients who have missed appointments, a credit card is kept on file,” he says.
In a practice similar to Dr. Beech, Dr. Goodman notes that he shows some flexibility for new patients when they miss an appointment the first time. “By the second time, they know this is the policy. Having ADHD can be financially costly.”
He notes that about 10% of his patients, roughly one a day, cancel late or don’t show up for scheduled appointments: “We keep a waitlist, and if someone cancels before the appointment, we can often fill the time with another patient in need on our waitlist.”
Dr. Goodman noted repeatedly that the clinician needs to be able to empathize with the patient’s condition and how they suffer. “This is not something people choose to have. The trap is that people think that if you’re successful you can’t have ADHD, and that’s not true. Often people with this condition work harder, are brighter, and find ways to compensate.”
If a practice is set up to accommodate the needs of patients with attention and organizational issues, treating them can be very gratifying. In settings without administrative support, the psychiatrist needs to stay cognizant of this invisible disability and the frustration that may come with this disorder, not just for the patient, but also for the family, friends, and employers, and even for the psychiatrist.
Dr. Dinah Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, Baltimore. Dr. Miller has no conflicts of interest.
A version of this article first appeared on Medscape.com.
Maybe you know some of these patients: They may come late or not show up at all. They may have little to say and minimize their difficulties, often because they are ashamed of how much effort it takes to meet ordinary obligations. They may struggle to complete assignments, fail classes, or lose jobs. And being in the right place at the right time can feel monumental to them: They forget appointments, double book themselves, or sometimes sleep through important events.
It’s not just appointments. They lose their keys and valuables, forget to pay bills, and may not answer calls, texts, or emails. Their voicemail may be full and people are often frustrated with them. These are all characteristics of executive dysfunction, which together can make the routine responsibilities of life very difficult.
Treatments include stimulants, and because of their potential for abuse, these medications are more strictly regulated when it comes to prescribing. The FDA does not allow them to be phoned into a pharmacy or refills to be added to prescriptions. Patients must wait until right before they are due to run out to get the next prescription, and this can present a problem if the patient travels or takes long vacations.
And although it is not the patient’s fault that stimulants can’t be ordered with refills, this adds to the burden of treating patients who take them. It’s hard to imagine that these restrictions on stimulants and opiates (but not on benzodiazepines) do much to deter abuse or diversion.
I trained at a time when ADD and ADHD were disorders of childhood, and as an adult psychiatrist, I was not exposed to patients on these medications. Occasionally, a stimulant was prescribed in a low dose to help activate a very depressed patient, but it was thought that children outgrow issues of attention and focus, and I have never felt fully confident in the more nuanced use of these medications with adults. Most of the patients I now treat with ADD have come to me on stable doses of the medications or at least with a history that directs care.
With others, the tip-off to look for the disorder is their disorganization in the absence of a substance use or active mood disorder. Medications help, sometimes remarkably, yet patients still struggle with organization and planning, and sometimes I find myself frustrated when patients forget their appointments or the issues around prescribing stimulants become time-consuming.
David W. Goodman, MD, director of the Adult Attention Deficit Center of Maryland, Lutherville, currently treats hundreds of patients with ADD and has written and spoken extensively about treating this disorder in adults.
“There are three things that make it difficult to manage patients with ADD,” Dr. Goodman noted, referring specifically to administrative issues. “You can’t write for refills, but with e-prescribing you can write a sequence of prescriptions with ‘fill-after’ dates. Or some patients are able to get a 90-day supply from mail-order pharmacies. Still, it’s a hassle if the patient moves around, as college students often do, and there are inventory shortages when some pharmacies can’t get the medications.”
“The second issue,” he adds, “is that it’s the nature of this disorder that patients struggle with organizational issues. Yelling at someone with ADD to pay attention is like yelling at a blind person not to run into furniture when they are in a new room. They go through life with people being impatient that they can’t do the things an ordinary person can do easily.”
Finally, Dr. Goodman noted that the clinicians who treat patients with ADD may have counter-transference issues.
“You have to understand that this is a disability and be sympathetic to it. They often have comorbid disorders, including personality disorders, and this can all bleed over to cause frustrations in their care. Psychiatrists who treat patients with ADD need to know they can deal with them compassionately.”
“I am occasionally contacted by patients who already have an ADHD diagnosis and are on stimulants, and who seem like they just want to get their prescriptions filled and aren’t interested in working on their issues,” says Douglas Beech, MD, a psychiatrist in private practice in Worthington, Ohio. “The doctor in this situation can feel like they are functioning as a sort of drug dealer. There are logistical matters that are structurally inherent in trying to assist these patients, from both a regulatory perspective and from a functional perspective. Dr. Beech feels that it’s helpful to acknowledge these issues when seeing patients with ADHD, so that he is prepared when problems do arise.
“It can almost feel cruel to charge a patient for a “no-show,” when difficulty keeping appointments may be a symptom of their illness, Dr. Beech adds. But he does believe it’s important to apply any fee policy equitably to all patients. “I don’t apply the ‘missed appointment’ policy differently to a person with an ADHD diagnosis versus any other diagnosis.” Though for their first missed appointment, he does give patients a “mulligan.”
“I don’t charge, but it puts both patient and doctor on notice,” he says.
And when his patients do miss an appointment, he offers to send a reminder for the next time, which is he says is effective. “With electronic messaging, this is a quick and easy way to prevent missed appointments and the complications that arise with prescriptions and rescheduling,” says Dr. Beech.
Dr. Goodman speaks about manging a large caseload of patients, many of whom have organizational issues.
“I have a full-time office manager who handles a lot of the logistics of scheduling and prescribing. Patients are sent multiple reminders, and I charge a nominal administrative fee if prescriptions need to be sent outside of appointments. This is not to make money, but to encourage patients to consider the administrative time.”
“I charge for appointments that are not canceled 48 hours in advance, and for patients who have missed appointments, a credit card is kept on file,” he says.
In a practice similar to Dr. Beech, Dr. Goodman notes that he shows some flexibility for new patients when they miss an appointment the first time. “By the second time, they know this is the policy. Having ADHD can be financially costly.”
He notes that about 10% of his patients, roughly one a day, cancel late or don’t show up for scheduled appointments: “We keep a waitlist, and if someone cancels before the appointment, we can often fill the time with another patient in need on our waitlist.”
Dr. Goodman noted repeatedly that the clinician needs to be able to empathize with the patient’s condition and how they suffer. “This is not something people choose to have. The trap is that people think that if you’re successful you can’t have ADHD, and that’s not true. Often people with this condition work harder, are brighter, and find ways to compensate.”
If a practice is set up to accommodate the needs of patients with attention and organizational issues, treating them can be very gratifying. In settings without administrative support, the psychiatrist needs to stay cognizant of this invisible disability and the frustration that may come with this disorder, not just for the patient, but also for the family, friends, and employers, and even for the psychiatrist.
Dr. Dinah Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, Baltimore. Dr. Miller has no conflicts of interest.
A version of this article first appeared on Medscape.com.
Poorest children at higher risk for PICU admissions, death
SAN FRANCISCO – Children who live in neighborhoods that are at the bottom of the socioeconomic ladder are at significantly greater risk for being admitted to a pediatric intensive care unit (PICU) and of dying there, a study of Medicaid data showed.
Among more than 4 million children and adolescents in 12 U.S. states, those in the most socioeconomically deprived quartile had a significantly higher risk for PICU admission and in-hospital death, compared with patients from the least-deprived areas.
Black children were also at significantly higher risk for death than children of other races, reported Hannah K. Mitchell, BMBS, MSc, from Evelina Children’s Hospital, London.“I think we need to do better work for trying to understand the mechanisms behind these disparities, ... whether they can be intervened over in a hospital setting, and to try to identify targeted interventions,” she said during a presentation at the American Thoracic Society International Conference 2022.
Medicaid data
During her residency in pediatrics at Children’s Hospital of Philadelphia, Ms. Mitchell and colleagues conducted a study to determine whether there were disparities in PICU admissions and mortality according to socioeconomic deprivation in specific neighborhoods.
They created a retrospective cohort study of Medicaid patients from birth to age 20 who were covered from 2007 through 2014 in 12 U.S. states, using ZIP codes to identify areas of social deprivation.
They restricted the analysis to children from households with annual incomes below 150% of the federal poverty line and divided the cohort into socioeconomic quartiles.
A total of nearly 4.1 million children and adolescents were included in the sample. Of this group, 274,782 were admitted to a PICU during the study period.
The median age of children admitted to a PICU was 4 years (interquartile range 0-15), and slightly more than two-thirds (68.5%) had a chronic complex condition.
In all, 43.5% were identified as White, and 32.1% were identified as Black. Ms. Mitchell noted that one of the limitations of the study was missing data on patients of Hispanic/Latinx origin.
The mortality rate among all patients admitted to a PICU was 2.5%.
In univariate logistic regression analysis, the odds ratio for PICU admission among children living in the most impoverished circumstances was 1.21 (P < .0001).
Among all patients admitted to a PICU, the OR for death for children in the most deprived quartile, compared with the least deprived was 1.12 (P = .0047).
In addition, Black children were significantly more likely than White children to be admitted to a PICU (OR, 1.14; P < .0001) and to die in hospital (OR, 1.18, P < .0001).
Ms. Mitchell said that clinicians need to move beyond describing disparities and should instead begin to focus on interventions to eliminate or reduce them.
She noted that children in poor neighborhoods may be more likely to receive care in lower-quality hospitals or may be treated differently from other children when hospitalized because of their socioeconomic status.
Poor housing, environmental injustice
A pediatric pulmonary specialist who works in a safety net hospital told this news organization that there are multiple factors that contribute to increased risk for PICU admissions and mortality in disadvantaged neighborhoods.
“The overwhelming majority of our patients are not only of low socioeconomic status on an individual level but also live in areas of great socioeconomic deprivation, and all of those social determinants of health are resulting in increased admissions to the PICU,” said Robyn T. Cohen, MD, associate professor of pediatrics at Boston University Medical Center.
“They’re living in poor housing conditions with environmental pollution and experiencing competing priorities that prevent early access to care or the ability to obtain medications. We should be doing better to prevent that from happening” said Dr. Cohen, who co-moderated the session but was not involved with the study.
The study was supported by a grant from the National Institutes of Health. Ms. Mitchell and Dr. Cohen have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – Children who live in neighborhoods that are at the bottom of the socioeconomic ladder are at significantly greater risk for being admitted to a pediatric intensive care unit (PICU) and of dying there, a study of Medicaid data showed.
Among more than 4 million children and adolescents in 12 U.S. states, those in the most socioeconomically deprived quartile had a significantly higher risk for PICU admission and in-hospital death, compared with patients from the least-deprived areas.
Black children were also at significantly higher risk for death than children of other races, reported Hannah K. Mitchell, BMBS, MSc, from Evelina Children’s Hospital, London.“I think we need to do better work for trying to understand the mechanisms behind these disparities, ... whether they can be intervened over in a hospital setting, and to try to identify targeted interventions,” she said during a presentation at the American Thoracic Society International Conference 2022.
Medicaid data
During her residency in pediatrics at Children’s Hospital of Philadelphia, Ms. Mitchell and colleagues conducted a study to determine whether there were disparities in PICU admissions and mortality according to socioeconomic deprivation in specific neighborhoods.
They created a retrospective cohort study of Medicaid patients from birth to age 20 who were covered from 2007 through 2014 in 12 U.S. states, using ZIP codes to identify areas of social deprivation.
They restricted the analysis to children from households with annual incomes below 150% of the federal poverty line and divided the cohort into socioeconomic quartiles.
A total of nearly 4.1 million children and adolescents were included in the sample. Of this group, 274,782 were admitted to a PICU during the study period.
The median age of children admitted to a PICU was 4 years (interquartile range 0-15), and slightly more than two-thirds (68.5%) had a chronic complex condition.
In all, 43.5% were identified as White, and 32.1% were identified as Black. Ms. Mitchell noted that one of the limitations of the study was missing data on patients of Hispanic/Latinx origin.
The mortality rate among all patients admitted to a PICU was 2.5%.
In univariate logistic regression analysis, the odds ratio for PICU admission among children living in the most impoverished circumstances was 1.21 (P < .0001).
Among all patients admitted to a PICU, the OR for death for children in the most deprived quartile, compared with the least deprived was 1.12 (P = .0047).
In addition, Black children were significantly more likely than White children to be admitted to a PICU (OR, 1.14; P < .0001) and to die in hospital (OR, 1.18, P < .0001).
Ms. Mitchell said that clinicians need to move beyond describing disparities and should instead begin to focus on interventions to eliminate or reduce them.
She noted that children in poor neighborhoods may be more likely to receive care in lower-quality hospitals or may be treated differently from other children when hospitalized because of their socioeconomic status.
Poor housing, environmental injustice
A pediatric pulmonary specialist who works in a safety net hospital told this news organization that there are multiple factors that contribute to increased risk for PICU admissions and mortality in disadvantaged neighborhoods.
“The overwhelming majority of our patients are not only of low socioeconomic status on an individual level but also live in areas of great socioeconomic deprivation, and all of those social determinants of health are resulting in increased admissions to the PICU,” said Robyn T. Cohen, MD, associate professor of pediatrics at Boston University Medical Center.
“They’re living in poor housing conditions with environmental pollution and experiencing competing priorities that prevent early access to care or the ability to obtain medications. We should be doing better to prevent that from happening” said Dr. Cohen, who co-moderated the session but was not involved with the study.
The study was supported by a grant from the National Institutes of Health. Ms. Mitchell and Dr. Cohen have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – Children who live in neighborhoods that are at the bottom of the socioeconomic ladder are at significantly greater risk for being admitted to a pediatric intensive care unit (PICU) and of dying there, a study of Medicaid data showed.
Among more than 4 million children and adolescents in 12 U.S. states, those in the most socioeconomically deprived quartile had a significantly higher risk for PICU admission and in-hospital death, compared with patients from the least-deprived areas.
Black children were also at significantly higher risk for death than children of other races, reported Hannah K. Mitchell, BMBS, MSc, from Evelina Children’s Hospital, London.“I think we need to do better work for trying to understand the mechanisms behind these disparities, ... whether they can be intervened over in a hospital setting, and to try to identify targeted interventions,” she said during a presentation at the American Thoracic Society International Conference 2022.
Medicaid data
During her residency in pediatrics at Children’s Hospital of Philadelphia, Ms. Mitchell and colleagues conducted a study to determine whether there were disparities in PICU admissions and mortality according to socioeconomic deprivation in specific neighborhoods.
They created a retrospective cohort study of Medicaid patients from birth to age 20 who were covered from 2007 through 2014 in 12 U.S. states, using ZIP codes to identify areas of social deprivation.
They restricted the analysis to children from households with annual incomes below 150% of the federal poverty line and divided the cohort into socioeconomic quartiles.
A total of nearly 4.1 million children and adolescents were included in the sample. Of this group, 274,782 were admitted to a PICU during the study period.
The median age of children admitted to a PICU was 4 years (interquartile range 0-15), and slightly more than two-thirds (68.5%) had a chronic complex condition.
In all, 43.5% were identified as White, and 32.1% were identified as Black. Ms. Mitchell noted that one of the limitations of the study was missing data on patients of Hispanic/Latinx origin.
The mortality rate among all patients admitted to a PICU was 2.5%.
In univariate logistic regression analysis, the odds ratio for PICU admission among children living in the most impoverished circumstances was 1.21 (P < .0001).
Among all patients admitted to a PICU, the OR for death for children in the most deprived quartile, compared with the least deprived was 1.12 (P = .0047).
In addition, Black children were significantly more likely than White children to be admitted to a PICU (OR, 1.14; P < .0001) and to die in hospital (OR, 1.18, P < .0001).
Ms. Mitchell said that clinicians need to move beyond describing disparities and should instead begin to focus on interventions to eliminate or reduce them.
She noted that children in poor neighborhoods may be more likely to receive care in lower-quality hospitals or may be treated differently from other children when hospitalized because of their socioeconomic status.
Poor housing, environmental injustice
A pediatric pulmonary specialist who works in a safety net hospital told this news organization that there are multiple factors that contribute to increased risk for PICU admissions and mortality in disadvantaged neighborhoods.
“The overwhelming majority of our patients are not only of low socioeconomic status on an individual level but also live in areas of great socioeconomic deprivation, and all of those social determinants of health are resulting in increased admissions to the PICU,” said Robyn T. Cohen, MD, associate professor of pediatrics at Boston University Medical Center.
“They’re living in poor housing conditions with environmental pollution and experiencing competing priorities that prevent early access to care or the ability to obtain medications. We should be doing better to prevent that from happening” said Dr. Cohen, who co-moderated the session but was not involved with the study.
The study was supported by a grant from the National Institutes of Health. Ms. Mitchell and Dr. Cohen have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Keeping thyroid hormone treatment on target is key for the heart
A new study highlights the importance of avoiding both exogenous hyperthyroidism and exogenous hypothyroidism to decrease cardiovascular risk and death among patients receiving thyroid hormone treatment.
“Our findings suggest that clinicians should make every effort to maintain euthyroidism in patients on thyroid hormone treatment, regardless of underlying cardiovascular risk, particularly in vulnerable populations, such as older adults,” senior author Maria Papaleontiou, MD, said in an interview.
Commenting on the study, David S. Cooper, MD, of Johns Hopkins University School of Medicine, Baltimore, agreed that the findings are significant.
“Both undertreatment and overtreatment were associated with adverse cardiovascular outcomes, meaning that patients’ thyroid function needs to be monitored, and levothyroxine adjusted if need be, on an ongoing basis,” he told this news organization.
Getting the balance right: a tricky task
Variations in thyroid hormone levels falling above or below target ranges are common with thyroid hormone therapy, as a wide array of factors can prompt the need to regularly adjust dosing to maintain “index” levels. And while guidelines from the American Thyroid Association (ATA) recommend maintaining serum thyroid stimulating hormone (TSH) levels in the normal ranges during treatment, the task is tricky.
“Despite these [ATA] guidelines, prior studies in adults with hypothyroidism have shown that up to 30% are undertreated and up to 48% are overtreated,” said Dr. Papaleontiou, an assistant professor in the Division of Metabolism, Endocrinology at the University of Michigan, Ann Arbor.
In a previous study, Dr. Papaleontiou and colleagues showed that the intensity of thyroid hormone treatment is a modifiable risk factor for incident atrial fibrillation and stroke, however, less is understood about the association with cardiovascular mortality.
For the new study, published in JAMA Network Open, Josh M. Evron, MD, of the University of North Carolina, Chapel Hill, and colleagues further investigated the issue in a large, retrospective cohort of 705,307 adults in the Veterans Health Administration Corporate Data Warehouse treated with thyroid hormone during 2004-2017 who had a median follow-up of 4 years.
They investigated the roles of TSH as well as free thyroxine (FT4) levels among 701,929 adults in the group with data on TSH and 373,981 patients with FT4 measurements.
The mean age of participants was 67 years and 88.7% were male.
Over the course of the study, 10.8% of patients (75,963) died of cardiovascular causes.
Compared with patients with normal thyroid levels, those with exogenous hyperthyroidism related to thyroid hormone treatment had an increased risk of cardiovascular mortality, specifically including when TSH levels were below 0.1 mIU/L (adjusted hazard ratio, 1.39) and when FT4 levels were above 1.9 ng/dL (AHR, 1.29), independent of factors including age, sex, and traditional cardiovascular risk factors, including hypertension, smoking, and previous cardiovascular disease or arrhythmia.
In addition, the increased risk of cardiovascular mortality was observed with exogenous hypothyroidism, specifically among those with TSH levels above 20 mIU/L (AHR, 2.67) and FT4 levels below 0.7 ng/dL (AHR, 1.56), after multivariate adjustment.
Of note, the risk of cardiovascular mortality was dose-dependent, with the risk increasing progressively with the lower and higher TSH levels, compared with normal levels.
The increased mortality risk in relation to TSH levels was more pronounced among older patients, compared with FT4 associations, the authors note.
“From a clinical perspective, older adults, and particularly the oldest old (aged 85 years), appear to be the most vulnerable, with increased risk of cardiovascular mortality with both exogenous hyperthyroidism and hypothyroidism,” they report.
Among key limitations is that women, who make up the majority of patients with thyroid disease, are under-represented in the predominantly male population of the Veterans Health Administration.
Nevertheless, “because the risk of cardiovascular disease is higher for men than for women, and because more than 70,000 women were included in this cohort, the results of this study are highly clinically relevant,” the authors note.
Addressing over- and under-treatment will avoid harm
The results are also important considering the status of levothyroxine (for hypothyroidism) as consistently ranking among the top three prescription medications in the United States.
And with the common occurrence of exogenous hyperthyroidism or hypothyroidism, the findings have important implications.
“Addressing over- and under-treatment of hypothyroidism promptly will help reduce patient harm, particularly in vulnerable populations such as older adults who are at higher risk for adverse effects,” Dr. Papaleontiou said.
Dr. Cooper further commented that the findings underscore the need to be aware of treatment adjustments and targets that may vary according to patient age.
“In older persons, over 65-70, the target TSH may be higher [for example, 2-4 mIU/L] than in younger persons, and in patients above ages 70 or 80, serum TSH levels may be allowed to rise even further into the 4-6 mIU/L range,” he explained.
“The older the patient, the higher the chance for an adverse cardiovascular outcome if the TSH is subnormal due to iatrogenic thyrotoxicosis,” Dr. Cooper explained.
“In contrast, in younger individuals, an elevated TSH, indicating mild [subclinical] hypothyroidism may be associated with increased cardiovascular risk, especially with serum TSH levels greater than 7 mIU/L.”
The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new study highlights the importance of avoiding both exogenous hyperthyroidism and exogenous hypothyroidism to decrease cardiovascular risk and death among patients receiving thyroid hormone treatment.
“Our findings suggest that clinicians should make every effort to maintain euthyroidism in patients on thyroid hormone treatment, regardless of underlying cardiovascular risk, particularly in vulnerable populations, such as older adults,” senior author Maria Papaleontiou, MD, said in an interview.
Commenting on the study, David S. Cooper, MD, of Johns Hopkins University School of Medicine, Baltimore, agreed that the findings are significant.
“Both undertreatment and overtreatment were associated with adverse cardiovascular outcomes, meaning that patients’ thyroid function needs to be monitored, and levothyroxine adjusted if need be, on an ongoing basis,” he told this news organization.
Getting the balance right: a tricky task
Variations in thyroid hormone levels falling above or below target ranges are common with thyroid hormone therapy, as a wide array of factors can prompt the need to regularly adjust dosing to maintain “index” levels. And while guidelines from the American Thyroid Association (ATA) recommend maintaining serum thyroid stimulating hormone (TSH) levels in the normal ranges during treatment, the task is tricky.
“Despite these [ATA] guidelines, prior studies in adults with hypothyroidism have shown that up to 30% are undertreated and up to 48% are overtreated,” said Dr. Papaleontiou, an assistant professor in the Division of Metabolism, Endocrinology at the University of Michigan, Ann Arbor.
In a previous study, Dr. Papaleontiou and colleagues showed that the intensity of thyroid hormone treatment is a modifiable risk factor for incident atrial fibrillation and stroke, however, less is understood about the association with cardiovascular mortality.
For the new study, published in JAMA Network Open, Josh M. Evron, MD, of the University of North Carolina, Chapel Hill, and colleagues further investigated the issue in a large, retrospective cohort of 705,307 adults in the Veterans Health Administration Corporate Data Warehouse treated with thyroid hormone during 2004-2017 who had a median follow-up of 4 years.
They investigated the roles of TSH as well as free thyroxine (FT4) levels among 701,929 adults in the group with data on TSH and 373,981 patients with FT4 measurements.
The mean age of participants was 67 years and 88.7% were male.
Over the course of the study, 10.8% of patients (75,963) died of cardiovascular causes.
Compared with patients with normal thyroid levels, those with exogenous hyperthyroidism related to thyroid hormone treatment had an increased risk of cardiovascular mortality, specifically including when TSH levels were below 0.1 mIU/L (adjusted hazard ratio, 1.39) and when FT4 levels were above 1.9 ng/dL (AHR, 1.29), independent of factors including age, sex, and traditional cardiovascular risk factors, including hypertension, smoking, and previous cardiovascular disease or arrhythmia.
In addition, the increased risk of cardiovascular mortality was observed with exogenous hypothyroidism, specifically among those with TSH levels above 20 mIU/L (AHR, 2.67) and FT4 levels below 0.7 ng/dL (AHR, 1.56), after multivariate adjustment.
Of note, the risk of cardiovascular mortality was dose-dependent, with the risk increasing progressively with the lower and higher TSH levels, compared with normal levels.
The increased mortality risk in relation to TSH levels was more pronounced among older patients, compared with FT4 associations, the authors note.
“From a clinical perspective, older adults, and particularly the oldest old (aged 85 years), appear to be the most vulnerable, with increased risk of cardiovascular mortality with both exogenous hyperthyroidism and hypothyroidism,” they report.
Among key limitations is that women, who make up the majority of patients with thyroid disease, are under-represented in the predominantly male population of the Veterans Health Administration.
Nevertheless, “because the risk of cardiovascular disease is higher for men than for women, and because more than 70,000 women were included in this cohort, the results of this study are highly clinically relevant,” the authors note.
Addressing over- and under-treatment will avoid harm
The results are also important considering the status of levothyroxine (for hypothyroidism) as consistently ranking among the top three prescription medications in the United States.
And with the common occurrence of exogenous hyperthyroidism or hypothyroidism, the findings have important implications.
“Addressing over- and under-treatment of hypothyroidism promptly will help reduce patient harm, particularly in vulnerable populations such as older adults who are at higher risk for adverse effects,” Dr. Papaleontiou said.
Dr. Cooper further commented that the findings underscore the need to be aware of treatment adjustments and targets that may vary according to patient age.
“In older persons, over 65-70, the target TSH may be higher [for example, 2-4 mIU/L] than in younger persons, and in patients above ages 70 or 80, serum TSH levels may be allowed to rise even further into the 4-6 mIU/L range,” he explained.
“The older the patient, the higher the chance for an adverse cardiovascular outcome if the TSH is subnormal due to iatrogenic thyrotoxicosis,” Dr. Cooper explained.
“In contrast, in younger individuals, an elevated TSH, indicating mild [subclinical] hypothyroidism may be associated with increased cardiovascular risk, especially with serum TSH levels greater than 7 mIU/L.”
The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new study highlights the importance of avoiding both exogenous hyperthyroidism and exogenous hypothyroidism to decrease cardiovascular risk and death among patients receiving thyroid hormone treatment.
“Our findings suggest that clinicians should make every effort to maintain euthyroidism in patients on thyroid hormone treatment, regardless of underlying cardiovascular risk, particularly in vulnerable populations, such as older adults,” senior author Maria Papaleontiou, MD, said in an interview.
Commenting on the study, David S. Cooper, MD, of Johns Hopkins University School of Medicine, Baltimore, agreed that the findings are significant.
“Both undertreatment and overtreatment were associated with adverse cardiovascular outcomes, meaning that patients’ thyroid function needs to be monitored, and levothyroxine adjusted if need be, on an ongoing basis,” he told this news organization.
Getting the balance right: a tricky task
Variations in thyroid hormone levels falling above or below target ranges are common with thyroid hormone therapy, as a wide array of factors can prompt the need to regularly adjust dosing to maintain “index” levels. And while guidelines from the American Thyroid Association (ATA) recommend maintaining serum thyroid stimulating hormone (TSH) levels in the normal ranges during treatment, the task is tricky.
“Despite these [ATA] guidelines, prior studies in adults with hypothyroidism have shown that up to 30% are undertreated and up to 48% are overtreated,” said Dr. Papaleontiou, an assistant professor in the Division of Metabolism, Endocrinology at the University of Michigan, Ann Arbor.
In a previous study, Dr. Papaleontiou and colleagues showed that the intensity of thyroid hormone treatment is a modifiable risk factor for incident atrial fibrillation and stroke, however, less is understood about the association with cardiovascular mortality.
For the new study, published in JAMA Network Open, Josh M. Evron, MD, of the University of North Carolina, Chapel Hill, and colleagues further investigated the issue in a large, retrospective cohort of 705,307 adults in the Veterans Health Administration Corporate Data Warehouse treated with thyroid hormone during 2004-2017 who had a median follow-up of 4 years.
They investigated the roles of TSH as well as free thyroxine (FT4) levels among 701,929 adults in the group with data on TSH and 373,981 patients with FT4 measurements.
The mean age of participants was 67 years and 88.7% were male.
Over the course of the study, 10.8% of patients (75,963) died of cardiovascular causes.
Compared with patients with normal thyroid levels, those with exogenous hyperthyroidism related to thyroid hormone treatment had an increased risk of cardiovascular mortality, specifically including when TSH levels were below 0.1 mIU/L (adjusted hazard ratio, 1.39) and when FT4 levels were above 1.9 ng/dL (AHR, 1.29), independent of factors including age, sex, and traditional cardiovascular risk factors, including hypertension, smoking, and previous cardiovascular disease or arrhythmia.
In addition, the increased risk of cardiovascular mortality was observed with exogenous hypothyroidism, specifically among those with TSH levels above 20 mIU/L (AHR, 2.67) and FT4 levels below 0.7 ng/dL (AHR, 1.56), after multivariate adjustment.
Of note, the risk of cardiovascular mortality was dose-dependent, with the risk increasing progressively with the lower and higher TSH levels, compared with normal levels.
The increased mortality risk in relation to TSH levels was more pronounced among older patients, compared with FT4 associations, the authors note.
“From a clinical perspective, older adults, and particularly the oldest old (aged 85 years), appear to be the most vulnerable, with increased risk of cardiovascular mortality with both exogenous hyperthyroidism and hypothyroidism,” they report.
Among key limitations is that women, who make up the majority of patients with thyroid disease, are under-represented in the predominantly male population of the Veterans Health Administration.
Nevertheless, “because the risk of cardiovascular disease is higher for men than for women, and because more than 70,000 women were included in this cohort, the results of this study are highly clinically relevant,” the authors note.
Addressing over- and under-treatment will avoid harm
The results are also important considering the status of levothyroxine (for hypothyroidism) as consistently ranking among the top three prescription medications in the United States.
And with the common occurrence of exogenous hyperthyroidism or hypothyroidism, the findings have important implications.
“Addressing over- and under-treatment of hypothyroidism promptly will help reduce patient harm, particularly in vulnerable populations such as older adults who are at higher risk for adverse effects,” Dr. Papaleontiou said.
Dr. Cooper further commented that the findings underscore the need to be aware of treatment adjustments and targets that may vary according to patient age.
“In older persons, over 65-70, the target TSH may be higher [for example, 2-4 mIU/L] than in younger persons, and in patients above ages 70 or 80, serum TSH levels may be allowed to rise even further into the 4-6 mIU/L range,” he explained.
“The older the patient, the higher the chance for an adverse cardiovascular outcome if the TSH is subnormal due to iatrogenic thyrotoxicosis,” Dr. Cooper explained.
“In contrast, in younger individuals, an elevated TSH, indicating mild [subclinical] hypothyroidism may be associated with increased cardiovascular risk, especially with serum TSH levels greater than 7 mIU/L.”
The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Omicron breakthrough cases boost protection, studies say
two preprint studies show.
The University of Washington, Seattle, working with Vir Biotechnology of San Francisco, looked at blood samples of vaccinated people who had breakthrough cases of Delta or Omicron and compared the samples with three other groups: people who caught COVID and were later vaccinated, vaccinated people who were never infected, and people who were infected and never vaccinated.
The vaccinated people who had a breakthrough case of Omicron produced antibodies that helped protect against coronavirus variants, whereas unvaccinated people who caught Omicron didn’t produce as many antibodies, the study showed.
BioNTech, the German biotechnology company, found that people who’d been double and triple vaccinated and then became infected with Omicron had a better B-cell response than people who’d gotten a booster shot but had not been infected.
The University of Washington research team also came up with similar findings about B cells.
The findings don’t mean people should deliberately try to become infected with COVID, said Alexandra Walls, PhD, one of the University of Washington scientists, according to Business Standard.
But the study does indicate “that we are at the point where we may want to consider having a different vaccine to boost people,” said David Veesler, PhD, of the University of Washington team.
“We should think about breakthrough infections as essentially equivalent to another dose of vaccine,” John Wherry, PhD, a professor and director of the Institute for Immunology at the University of Pennsylvania, Philadelphia, told Business Standard. Dr. Wherry was not involved in the studies but reviewed the BioNTech study.
A version of this article first appeared on WebMD.com.
two preprint studies show.
The University of Washington, Seattle, working with Vir Biotechnology of San Francisco, looked at blood samples of vaccinated people who had breakthrough cases of Delta or Omicron and compared the samples with three other groups: people who caught COVID and were later vaccinated, vaccinated people who were never infected, and people who were infected and never vaccinated.
The vaccinated people who had a breakthrough case of Omicron produced antibodies that helped protect against coronavirus variants, whereas unvaccinated people who caught Omicron didn’t produce as many antibodies, the study showed.
BioNTech, the German biotechnology company, found that people who’d been double and triple vaccinated and then became infected with Omicron had a better B-cell response than people who’d gotten a booster shot but had not been infected.
The University of Washington research team also came up with similar findings about B cells.
The findings don’t mean people should deliberately try to become infected with COVID, said Alexandra Walls, PhD, one of the University of Washington scientists, according to Business Standard.
But the study does indicate “that we are at the point where we may want to consider having a different vaccine to boost people,” said David Veesler, PhD, of the University of Washington team.
“We should think about breakthrough infections as essentially equivalent to another dose of vaccine,” John Wherry, PhD, a professor and director of the Institute for Immunology at the University of Pennsylvania, Philadelphia, told Business Standard. Dr. Wherry was not involved in the studies but reviewed the BioNTech study.
A version of this article first appeared on WebMD.com.
two preprint studies show.
The University of Washington, Seattle, working with Vir Biotechnology of San Francisco, looked at blood samples of vaccinated people who had breakthrough cases of Delta or Omicron and compared the samples with three other groups: people who caught COVID and were later vaccinated, vaccinated people who were never infected, and people who were infected and never vaccinated.
The vaccinated people who had a breakthrough case of Omicron produced antibodies that helped protect against coronavirus variants, whereas unvaccinated people who caught Omicron didn’t produce as many antibodies, the study showed.
BioNTech, the German biotechnology company, found that people who’d been double and triple vaccinated and then became infected with Omicron had a better B-cell response than people who’d gotten a booster shot but had not been infected.
The University of Washington research team also came up with similar findings about B cells.
The findings don’t mean people should deliberately try to become infected with COVID, said Alexandra Walls, PhD, one of the University of Washington scientists, according to Business Standard.
But the study does indicate “that we are at the point where we may want to consider having a different vaccine to boost people,” said David Veesler, PhD, of the University of Washington team.
“We should think about breakthrough infections as essentially equivalent to another dose of vaccine,” John Wherry, PhD, a professor and director of the Institute for Immunology at the University of Pennsylvania, Philadelphia, told Business Standard. Dr. Wherry was not involved in the studies but reviewed the BioNTech study.
A version of this article first appeared on WebMD.com.
Doctor accused of ‘fraudulent concealment’ can’t be held liable
In April, the Iowa Supreme Court dismissed a knotty claim against a local doctor and hospital accused of concealing a woman’s renal cancer, according to a story in the Iowa Capital Dispatch, among other news outlets.
In 2004, Linda Berry visited Mercy Medical Center in Cedar Rapids for an unspecified ailment. At the hospital, Ms. Berry underwent a CT scan, which revealed a benign cyst on her right kidney.
The first of these four visits occurred in 2006, when Ms. Berry was again seen at Mercy, this time for a urinary tract infection. Despite undergoing a second renal scan, Ms. Berry was not informed of the mass on her right kidney.
Three years later, in October 2009, she arrived with her daughter at the Mercy emergency department (ED) complaining of abdominal pain. She was examined by Paul Grossmann, MD, a general surgeon. Ms. Berry underwent an abdominal scan that showed her renal abnormality. Dr. Grossmann diagnosed her as having constipation and released her from the ED. According to the family, he made no mention of the mass on her right kidney.
En route home, however, Ms. Berry and her daughter received a call from a resident under Dr. Grossmann’s supervision. Returning to the hospital, Ms. Berry learned that her constipation was actually colitis. She was prescribed an antibiotic and was again released from the ED. Her post-release instructions made no mention of the now larger mass on her kidney.
Two days later, still complaining of abdominal pain, Ms. Berry returned to the Mercy ED. Examined by another ED doctor, she underwent a fourth CT scan, which also showed the kidney mass. A radiology report urged Dr. Grossmann, her previous physician, to pursue the matter in order to rule out renal cancer. Dr. Grossmann followed up with Berry’s primary care doctor. In doing so, though, he mentioned only the patient’s ongoing colitis, not her kidney mass, according to the plaintiffs’ claim.
In 2016, following a fall, Ms. Berry returned yet again to the Mercy ED, this time with a broken arm. During her treatment, she underwent a fifth CT scan, which revealed the same kidney mass. This time, though, a discharge nurse mentioned the abnormality to Ms. Berry — allegedly the first time in more than a decade that a medical professional had alerted her to the potential problem.
The alert may have been too late, however. Ms. Berry was diagnosed shortly thereafter with metastatic renal cell carcinoma. She died on May 22, 2019.
Before her death, Ms. Berry filed a suit against Dr. Grossmann, Mercy, and its parent company, Catholic Health Initiatives. After her death, her family continued her claim.
By this point, more than a decade had passed since the alleged medical negligence first occurred. This time frame placed the Berry family’s claim outside of Iowa’s 6-year statute of limitations. Citing this fact, Dr. Grossmann, Mercy, and Catholic Health Initiatives sought to have the suit dismissed.
But Ms. Berry’s family stood their ground: Noting that the statute permitted an exception in cases in which the original negligence had been fraudulently concealed, the family argued that its suit move forward.
They encountered a roadblock, however, in district court, which ruled that the plaintiffs had failed to identify the alleged fraudulent concealment as separate from the alleged acts of medical negligence, which the 6-year filing exception required. Having failed in their claim to distinguish concealment from medical negligence, the plaintiffs would not be allowed to proceed with their suit.
The Berry family then asked the Iowa Court of Appeals to review the district court decision. In its review, the appeals court found that the lower court had erred when it disallowed the suit from moving forward. The Berry suit would once again be permitted to continue.
And that’s where matters stood until late last month, when the Iowa Supreme Court weighed in, stating: “The liability-producing conduct was Grossmann’s alleged failure to disclose to Berry the concerning findings on her CT scan. ... But the plaintiffs then rely on these same acts...as his acts of concealment,” which were simply “successive occasions” on which he was said to have acted negligently.
In light of this, argued the high-court justices, the Berry case effectively hinged not on allegations of fraudulent concealment but of medical negligence. And since the state’s statute of limitations was explicit in indicating that such negligence suits had to be brought within the 6-year filing deadline, the lower-court ruling stood, and the Berry case was dismissed.
A version of this article first appeared on Medscape.com.
In April, the Iowa Supreme Court dismissed a knotty claim against a local doctor and hospital accused of concealing a woman’s renal cancer, according to a story in the Iowa Capital Dispatch, among other news outlets.
In 2004, Linda Berry visited Mercy Medical Center in Cedar Rapids for an unspecified ailment. At the hospital, Ms. Berry underwent a CT scan, which revealed a benign cyst on her right kidney.
The first of these four visits occurred in 2006, when Ms. Berry was again seen at Mercy, this time for a urinary tract infection. Despite undergoing a second renal scan, Ms. Berry was not informed of the mass on her right kidney.
Three years later, in October 2009, she arrived with her daughter at the Mercy emergency department (ED) complaining of abdominal pain. She was examined by Paul Grossmann, MD, a general surgeon. Ms. Berry underwent an abdominal scan that showed her renal abnormality. Dr. Grossmann diagnosed her as having constipation and released her from the ED. According to the family, he made no mention of the mass on her right kidney.
En route home, however, Ms. Berry and her daughter received a call from a resident under Dr. Grossmann’s supervision. Returning to the hospital, Ms. Berry learned that her constipation was actually colitis. She was prescribed an antibiotic and was again released from the ED. Her post-release instructions made no mention of the now larger mass on her kidney.
Two days later, still complaining of abdominal pain, Ms. Berry returned to the Mercy ED. Examined by another ED doctor, she underwent a fourth CT scan, which also showed the kidney mass. A radiology report urged Dr. Grossmann, her previous physician, to pursue the matter in order to rule out renal cancer. Dr. Grossmann followed up with Berry’s primary care doctor. In doing so, though, he mentioned only the patient’s ongoing colitis, not her kidney mass, according to the plaintiffs’ claim.
In 2016, following a fall, Ms. Berry returned yet again to the Mercy ED, this time with a broken arm. During her treatment, she underwent a fifth CT scan, which revealed the same kidney mass. This time, though, a discharge nurse mentioned the abnormality to Ms. Berry — allegedly the first time in more than a decade that a medical professional had alerted her to the potential problem.
The alert may have been too late, however. Ms. Berry was diagnosed shortly thereafter with metastatic renal cell carcinoma. She died on May 22, 2019.
Before her death, Ms. Berry filed a suit against Dr. Grossmann, Mercy, and its parent company, Catholic Health Initiatives. After her death, her family continued her claim.
By this point, more than a decade had passed since the alleged medical negligence first occurred. This time frame placed the Berry family’s claim outside of Iowa’s 6-year statute of limitations. Citing this fact, Dr. Grossmann, Mercy, and Catholic Health Initiatives sought to have the suit dismissed.
But Ms. Berry’s family stood their ground: Noting that the statute permitted an exception in cases in which the original negligence had been fraudulently concealed, the family argued that its suit move forward.
They encountered a roadblock, however, in district court, which ruled that the plaintiffs had failed to identify the alleged fraudulent concealment as separate from the alleged acts of medical negligence, which the 6-year filing exception required. Having failed in their claim to distinguish concealment from medical negligence, the plaintiffs would not be allowed to proceed with their suit.
The Berry family then asked the Iowa Court of Appeals to review the district court decision. In its review, the appeals court found that the lower court had erred when it disallowed the suit from moving forward. The Berry suit would once again be permitted to continue.
And that’s where matters stood until late last month, when the Iowa Supreme Court weighed in, stating: “The liability-producing conduct was Grossmann’s alleged failure to disclose to Berry the concerning findings on her CT scan. ... But the plaintiffs then rely on these same acts...as his acts of concealment,” which were simply “successive occasions” on which he was said to have acted negligently.
In light of this, argued the high-court justices, the Berry case effectively hinged not on allegations of fraudulent concealment but of medical negligence. And since the state’s statute of limitations was explicit in indicating that such negligence suits had to be brought within the 6-year filing deadline, the lower-court ruling stood, and the Berry case was dismissed.
A version of this article first appeared on Medscape.com.
In April, the Iowa Supreme Court dismissed a knotty claim against a local doctor and hospital accused of concealing a woman’s renal cancer, according to a story in the Iowa Capital Dispatch, among other news outlets.
In 2004, Linda Berry visited Mercy Medical Center in Cedar Rapids for an unspecified ailment. At the hospital, Ms. Berry underwent a CT scan, which revealed a benign cyst on her right kidney.
The first of these four visits occurred in 2006, when Ms. Berry was again seen at Mercy, this time for a urinary tract infection. Despite undergoing a second renal scan, Ms. Berry was not informed of the mass on her right kidney.
Three years later, in October 2009, she arrived with her daughter at the Mercy emergency department (ED) complaining of abdominal pain. She was examined by Paul Grossmann, MD, a general surgeon. Ms. Berry underwent an abdominal scan that showed her renal abnormality. Dr. Grossmann diagnosed her as having constipation and released her from the ED. According to the family, he made no mention of the mass on her right kidney.
En route home, however, Ms. Berry and her daughter received a call from a resident under Dr. Grossmann’s supervision. Returning to the hospital, Ms. Berry learned that her constipation was actually colitis. She was prescribed an antibiotic and was again released from the ED. Her post-release instructions made no mention of the now larger mass on her kidney.
Two days later, still complaining of abdominal pain, Ms. Berry returned to the Mercy ED. Examined by another ED doctor, she underwent a fourth CT scan, which also showed the kidney mass. A radiology report urged Dr. Grossmann, her previous physician, to pursue the matter in order to rule out renal cancer. Dr. Grossmann followed up with Berry’s primary care doctor. In doing so, though, he mentioned only the patient’s ongoing colitis, not her kidney mass, according to the plaintiffs’ claim.
In 2016, following a fall, Ms. Berry returned yet again to the Mercy ED, this time with a broken arm. During her treatment, she underwent a fifth CT scan, which revealed the same kidney mass. This time, though, a discharge nurse mentioned the abnormality to Ms. Berry — allegedly the first time in more than a decade that a medical professional had alerted her to the potential problem.
The alert may have been too late, however. Ms. Berry was diagnosed shortly thereafter with metastatic renal cell carcinoma. She died on May 22, 2019.
Before her death, Ms. Berry filed a suit against Dr. Grossmann, Mercy, and its parent company, Catholic Health Initiatives. After her death, her family continued her claim.
By this point, more than a decade had passed since the alleged medical negligence first occurred. This time frame placed the Berry family’s claim outside of Iowa’s 6-year statute of limitations. Citing this fact, Dr. Grossmann, Mercy, and Catholic Health Initiatives sought to have the suit dismissed.
But Ms. Berry’s family stood their ground: Noting that the statute permitted an exception in cases in which the original negligence had been fraudulently concealed, the family argued that its suit move forward.
They encountered a roadblock, however, in district court, which ruled that the plaintiffs had failed to identify the alleged fraudulent concealment as separate from the alleged acts of medical negligence, which the 6-year filing exception required. Having failed in their claim to distinguish concealment from medical negligence, the plaintiffs would not be allowed to proceed with their suit.
The Berry family then asked the Iowa Court of Appeals to review the district court decision. In its review, the appeals court found that the lower court had erred when it disallowed the suit from moving forward. The Berry suit would once again be permitted to continue.
And that’s where matters stood until late last month, when the Iowa Supreme Court weighed in, stating: “The liability-producing conduct was Grossmann’s alleged failure to disclose to Berry the concerning findings on her CT scan. ... But the plaintiffs then rely on these same acts...as his acts of concealment,” which were simply “successive occasions” on which he was said to have acted negligently.
In light of this, argued the high-court justices, the Berry case effectively hinged not on allegations of fraudulent concealment but of medical negligence. And since the state’s statute of limitations was explicit in indicating that such negligence suits had to be brought within the 6-year filing deadline, the lower-court ruling stood, and the Berry case was dismissed.
A version of this article first appeared on Medscape.com.
Student loan forgiveness plans exclude physicians
In the run up to the midterm elections in November, President Biden has warmed to student loan forgiveness. However, before even being proposed,
What was the plan?
During the 2020 election, student loan forgiveness was a hot topic as the COVID epidemic raged. The CARES Act has placed all federal student loans in forbearance, with no payments made and the interest rate set to 0% to prevent further accrual. While this was tremendously useful to 45 million borrowers around the country (including the author), nothing material was done to deal with the loans.
The Biden Administration’s approach at that time was multi-tiered and chaotic. Plans were put forward that either expanded Public Service Loan Forgiveness (PSLF) or capped it. Plans were put forward that either extended free undergraduate or severely limited it through Pell Grants. Unfortunately, that duality continues today, with current plans not having a clear goal or a target group of beneficiaries.
Necessary CARES Act extensions
The Biden Administration has attempted repeatedly to turn the student loan apparatus back on, restarting payments en masse. However, each time, they are beset by challenges, ranging from repeat COVID spikes to servicer withdrawals or macroeconomic indicators of a recession.
At each step, the administration has had little choice but to extend the CARES Act forbearance, lest they suffer retribution for hastily resuming payments for 45 million borrowers without the apparatus to do so. Two years ago, the major federal servicers laid off hundreds, if not thousands, of staffers responsible for payment processing, accounting, customer care, and taxation. Hiring, training, and staffing these positions is nontrivial.
The administration has been out of step with servicers such that three of the largest have chosen not to renew their contracts: Navient, MyFedLoan, and Granite State Management and Resources. This has left 15 million borrowers in the lurch, not knowing who their servicer is – and, even worse, losing track of qualifying payments toward programs like PSLF.
Avenues of forgiveness
There are two major pathways to forgiveness. It is widely believed that the executive branch has the authority to broadly forgive student loans under executive order and managed through the U.S. Department of Education.
The alternative is through congressional action, voting on forgiveness as an economic stimulus plan. There is little appetite in Congress for forgiveness, and prominent congresspeople like Senator Warren and Senator Schumer have both pushed the executive branch for forgiveness in recognition of this.
What has been proposed?
First, it’s important to state that as headline-grabbing as it is to see that $50,000 of forgiveness has been proposed, the reality is that President Biden has repeatedly stated that he will not be in favor of that level of forgiveness. Instead, the number most commonly being discussed is $10,000. This would represent an unprecedented amount of support, alleviating 35% of borrowers of all student debt.
The impact of proposed forgiveness plans for physicians
For the medical community, sadly, this doesn’t represent a significant amount of forgiveness. At graduation, the average MD has $203,000 in debt, and the average DO has $258,000 in debt. These numbers grow during residency for years before any meaningful payments are made.
Further weakening forgiveness plans for physicians has been two caps proposed by the administration in recent days. The first is an income cap of $125,000. While this would maintain forgiveness for nearly all residents and fellows, this would exclude nearly every practicing physician. The alternative to an income cap is specific exclusion of certain careers seen to be high-earning: doctors and lawyers.
The bottom line
Physicians are unlikely to be included in any forgiveness plans being proposed recently by the Biden Administration. If they are considered, it will be for exclusion from any forgiveness offered.
For physicians no longer eligible for PSLF, this exclusion needs to be considered in managing the student loan debt associated with becoming a doctor.
Dr. Palmer is a part-time instructor, department of pediatrics, Harvard Medical School, Boston, and staff physician, department of medical critical care, Boston Children’s Hospital. He disclosed that he serves as director for Panacea Financial.
A version of this article first appeared on Medscape.com.
In the run up to the midterm elections in November, President Biden has warmed to student loan forgiveness. However, before even being proposed,
What was the plan?
During the 2020 election, student loan forgiveness was a hot topic as the COVID epidemic raged. The CARES Act has placed all federal student loans in forbearance, with no payments made and the interest rate set to 0% to prevent further accrual. While this was tremendously useful to 45 million borrowers around the country (including the author), nothing material was done to deal with the loans.
The Biden Administration’s approach at that time was multi-tiered and chaotic. Plans were put forward that either expanded Public Service Loan Forgiveness (PSLF) or capped it. Plans were put forward that either extended free undergraduate or severely limited it through Pell Grants. Unfortunately, that duality continues today, with current plans not having a clear goal or a target group of beneficiaries.
Necessary CARES Act extensions
The Biden Administration has attempted repeatedly to turn the student loan apparatus back on, restarting payments en masse. However, each time, they are beset by challenges, ranging from repeat COVID spikes to servicer withdrawals or macroeconomic indicators of a recession.
At each step, the administration has had little choice but to extend the CARES Act forbearance, lest they suffer retribution for hastily resuming payments for 45 million borrowers without the apparatus to do so. Two years ago, the major federal servicers laid off hundreds, if not thousands, of staffers responsible for payment processing, accounting, customer care, and taxation. Hiring, training, and staffing these positions is nontrivial.
The administration has been out of step with servicers such that three of the largest have chosen not to renew their contracts: Navient, MyFedLoan, and Granite State Management and Resources. This has left 15 million borrowers in the lurch, not knowing who their servicer is – and, even worse, losing track of qualifying payments toward programs like PSLF.
Avenues of forgiveness
There are two major pathways to forgiveness. It is widely believed that the executive branch has the authority to broadly forgive student loans under executive order and managed through the U.S. Department of Education.
The alternative is through congressional action, voting on forgiveness as an economic stimulus plan. There is little appetite in Congress for forgiveness, and prominent congresspeople like Senator Warren and Senator Schumer have both pushed the executive branch for forgiveness in recognition of this.
What has been proposed?
First, it’s important to state that as headline-grabbing as it is to see that $50,000 of forgiveness has been proposed, the reality is that President Biden has repeatedly stated that he will not be in favor of that level of forgiveness. Instead, the number most commonly being discussed is $10,000. This would represent an unprecedented amount of support, alleviating 35% of borrowers of all student debt.
The impact of proposed forgiveness plans for physicians
For the medical community, sadly, this doesn’t represent a significant amount of forgiveness. At graduation, the average MD has $203,000 in debt, and the average DO has $258,000 in debt. These numbers grow during residency for years before any meaningful payments are made.
Further weakening forgiveness plans for physicians has been two caps proposed by the administration in recent days. The first is an income cap of $125,000. While this would maintain forgiveness for nearly all residents and fellows, this would exclude nearly every practicing physician. The alternative to an income cap is specific exclusion of certain careers seen to be high-earning: doctors and lawyers.
The bottom line
Physicians are unlikely to be included in any forgiveness plans being proposed recently by the Biden Administration. If they are considered, it will be for exclusion from any forgiveness offered.
For physicians no longer eligible for PSLF, this exclusion needs to be considered in managing the student loan debt associated with becoming a doctor.
Dr. Palmer is a part-time instructor, department of pediatrics, Harvard Medical School, Boston, and staff physician, department of medical critical care, Boston Children’s Hospital. He disclosed that he serves as director for Panacea Financial.
A version of this article first appeared on Medscape.com.
In the run up to the midterm elections in November, President Biden has warmed to student loan forgiveness. However, before even being proposed,
What was the plan?
During the 2020 election, student loan forgiveness was a hot topic as the COVID epidemic raged. The CARES Act has placed all federal student loans in forbearance, with no payments made and the interest rate set to 0% to prevent further accrual. While this was tremendously useful to 45 million borrowers around the country (including the author), nothing material was done to deal with the loans.
The Biden Administration’s approach at that time was multi-tiered and chaotic. Plans were put forward that either expanded Public Service Loan Forgiveness (PSLF) or capped it. Plans were put forward that either extended free undergraduate or severely limited it through Pell Grants. Unfortunately, that duality continues today, with current plans not having a clear goal or a target group of beneficiaries.
Necessary CARES Act extensions
The Biden Administration has attempted repeatedly to turn the student loan apparatus back on, restarting payments en masse. However, each time, they are beset by challenges, ranging from repeat COVID spikes to servicer withdrawals or macroeconomic indicators of a recession.
At each step, the administration has had little choice but to extend the CARES Act forbearance, lest they suffer retribution for hastily resuming payments for 45 million borrowers without the apparatus to do so. Two years ago, the major federal servicers laid off hundreds, if not thousands, of staffers responsible for payment processing, accounting, customer care, and taxation. Hiring, training, and staffing these positions is nontrivial.
The administration has been out of step with servicers such that three of the largest have chosen not to renew their contracts: Navient, MyFedLoan, and Granite State Management and Resources. This has left 15 million borrowers in the lurch, not knowing who their servicer is – and, even worse, losing track of qualifying payments toward programs like PSLF.
Avenues of forgiveness
There are two major pathways to forgiveness. It is widely believed that the executive branch has the authority to broadly forgive student loans under executive order and managed through the U.S. Department of Education.
The alternative is through congressional action, voting on forgiveness as an economic stimulus plan. There is little appetite in Congress for forgiveness, and prominent congresspeople like Senator Warren and Senator Schumer have both pushed the executive branch for forgiveness in recognition of this.
What has been proposed?
First, it’s important to state that as headline-grabbing as it is to see that $50,000 of forgiveness has been proposed, the reality is that President Biden has repeatedly stated that he will not be in favor of that level of forgiveness. Instead, the number most commonly being discussed is $10,000. This would represent an unprecedented amount of support, alleviating 35% of borrowers of all student debt.
The impact of proposed forgiveness plans for physicians
For the medical community, sadly, this doesn’t represent a significant amount of forgiveness. At graduation, the average MD has $203,000 in debt, and the average DO has $258,000 in debt. These numbers grow during residency for years before any meaningful payments are made.
Further weakening forgiveness plans for physicians has been two caps proposed by the administration in recent days. The first is an income cap of $125,000. While this would maintain forgiveness for nearly all residents and fellows, this would exclude nearly every practicing physician. The alternative to an income cap is specific exclusion of certain careers seen to be high-earning: doctors and lawyers.
The bottom line
Physicians are unlikely to be included in any forgiveness plans being proposed recently by the Biden Administration. If they are considered, it will be for exclusion from any forgiveness offered.
For physicians no longer eligible for PSLF, this exclusion needs to be considered in managing the student loan debt associated with becoming a doctor.
Dr. Palmer is a part-time instructor, department of pediatrics, Harvard Medical School, Boston, and staff physician, department of medical critical care, Boston Children’s Hospital. He disclosed that he serves as director for Panacea Financial.
A version of this article first appeared on Medscape.com.
ISCHEMIA substudy data don’t add up, cardiac surgeons say
A recent ISCHEMIA trial substudy is under scrutiny from surgeons for a data discrepancy, rekindling concerns about reliance on the landmark trial data in the latest coronary revascularization guidelines.
As previously reported, the main ISCHEMIA findings showed no significant benefit for an initial strategy of percutaneous coronary intervention (PCI) or coronary bypass graft surgery (CABG) over medical therapy in patients with stable moderate to severe ischemic heart disease.
The 2021 substudy by Reynolds et al. showed that coronary artery disease (CAD) severity, classified using the modified Duke Prognostic Index score, predicted 4-year mortality and myocardial infarction in the trial, whereas ischemia severity did not.
Cardiac surgeons Joseph F. Sabik III, MD, and Faisal Bakaeen, MD, however, spotted that only 40 patients are in the Duke category 6 group (three-vessel severe stenosis of at least 70% or two-vessel severe stenosis with a proximal left anterior descending lesion) in Supplemental tables 1 and 2, whereas 659 are in the main paper.
In addition, the Supplemental tables list the following:
- 659 patients in Duke group 5, not 894 as in the paper.
- 894 patients in Duke group 4, not 743 as in the paper.
- 743 patients in Duke group 3, not 179 as in the paper.
The surgeons penned a letter to Circulation early in April flagging the discrepancies, but say it was rejected April 15 because it was submitted outside the journal’s 6-week window for letters. They posted a public comment on the Remarq research platform, as advised by Circulation’s editorial office, and reached out directly to the authors and ISCHEMIA leadership.
“They just keep saying it’s a simple formatting error. Well, if it is a simple formatting error, then fix it,” Dr. Sabik, chair of surgery at University Hospitals Cleveland Medical Center, said in an interview. “But here we are now, a month later, and they still haven’t published our letter. Why? We’re the ones who identified the problem.”
Dr. Sabik said the accuracy of the data has important implications because the recent AHA/ACC/SCAI coronary revascularization guidelines used the ISCHEMIA data to downgrade the CABG recommendation for complex multivessel disease from class 1 to class 2B. Patients with a Duke 6 score are also typically the ones referred for CABG by today’s heart teams.
Several surgical societies have contested the guidelines, questioning whether the ISCHEMIA patients are truly reflective of those seen in clinical practice and questioning the decision to treat PCI and surgery as equivalent strategies to decrease ischemic events.
Dr. Bakaeen, from the Cleveland Clinic, told this news organization they don’t want a public battle over the data like the one that befell the EXCEL trial, and that it’s entirely possible the investigators might have inadvertently upgraded all the Duke score assignments by 1.
A systematic error, however, is more plausible than a formatting error, he said, because Supplemental tables 1 and 2 correspond exactly to the Duke 1 to Duke 7 sequence, suggesting the tables are correct and that the error might have occurred downstream, including in the manuscript.
The numbers should be consistent across all the ISCHEMIA manuscripts, Dr. Bakaeen added, but currently “don’t add up,” even after adjustment for different denominators, and especially for participants with left main disease.
They hope that publication of their letter, he said, will convince the authors to publicly share the data for patients in each of the seven modified Duke categories.
Lead author of the ISCHEMIA substudy, Harmony Reynolds, MD, New York (N.Y.) University Langone Health, told this news organization via email that as a result of a “formatting error in the transfer of data from the statistical output file to a Word document, data in Supplemental tables 1 and 2 were incorrect.”
She explained that they planned to present six, not seven, rows for the Duke score in the tables, collapsing the first two categories of nonobstructive disease (Duke 1-2), as they were in all other tables and figures. However, the Supplemental tables had incorrect row headings and because the Word program is designed to fill all available rows, it inserted the data from the output file into a seven-row table shell, duplicating the values for row 1 in the last row for left main disease of at least 50%.
“The data were correctly presented in the main manuscript tables and figures and in the remainder of the supplement, with a total of 659 patients in the subset with modified Duke prognostic index category 6 on coronary CT angiography,” Dr. Reynolds said.
She noted that Circulation will issue a correction. In addition, “we are in the process of preparing the data for public sharing soon. The data will include the Duke prognostic score at all levels.”
Circulation editor-in-chief Joseph A. Hill, MD, PhD, chief of cardiology at UT Southwestern Medical Center, Dallas, declined to be interviewed but confirmed via email that Dr. Bakaeen and Dr. Sabik’s letter and the correction will be published the week of May 16.
As for the delay, he said, “I received their reach-out just over 1 week ago, and per protocol, we conducted an internal evaluation of their allegations, which took a bit of time.”
A version of this article first appeared on Medscape.com.
A recent ISCHEMIA trial substudy is under scrutiny from surgeons for a data discrepancy, rekindling concerns about reliance on the landmark trial data in the latest coronary revascularization guidelines.
As previously reported, the main ISCHEMIA findings showed no significant benefit for an initial strategy of percutaneous coronary intervention (PCI) or coronary bypass graft surgery (CABG) over medical therapy in patients with stable moderate to severe ischemic heart disease.
The 2021 substudy by Reynolds et al. showed that coronary artery disease (CAD) severity, classified using the modified Duke Prognostic Index score, predicted 4-year mortality and myocardial infarction in the trial, whereas ischemia severity did not.
Cardiac surgeons Joseph F. Sabik III, MD, and Faisal Bakaeen, MD, however, spotted that only 40 patients are in the Duke category 6 group (three-vessel severe stenosis of at least 70% or two-vessel severe stenosis with a proximal left anterior descending lesion) in Supplemental tables 1 and 2, whereas 659 are in the main paper.
In addition, the Supplemental tables list the following:
- 659 patients in Duke group 5, not 894 as in the paper.
- 894 patients in Duke group 4, not 743 as in the paper.
- 743 patients in Duke group 3, not 179 as in the paper.
The surgeons penned a letter to Circulation early in April flagging the discrepancies, but say it was rejected April 15 because it was submitted outside the journal’s 6-week window for letters. They posted a public comment on the Remarq research platform, as advised by Circulation’s editorial office, and reached out directly to the authors and ISCHEMIA leadership.
“They just keep saying it’s a simple formatting error. Well, if it is a simple formatting error, then fix it,” Dr. Sabik, chair of surgery at University Hospitals Cleveland Medical Center, said in an interview. “But here we are now, a month later, and they still haven’t published our letter. Why? We’re the ones who identified the problem.”
Dr. Sabik said the accuracy of the data has important implications because the recent AHA/ACC/SCAI coronary revascularization guidelines used the ISCHEMIA data to downgrade the CABG recommendation for complex multivessel disease from class 1 to class 2B. Patients with a Duke 6 score are also typically the ones referred for CABG by today’s heart teams.
Several surgical societies have contested the guidelines, questioning whether the ISCHEMIA patients are truly reflective of those seen in clinical practice and questioning the decision to treat PCI and surgery as equivalent strategies to decrease ischemic events.
Dr. Bakaeen, from the Cleveland Clinic, told this news organization they don’t want a public battle over the data like the one that befell the EXCEL trial, and that it’s entirely possible the investigators might have inadvertently upgraded all the Duke score assignments by 1.
A systematic error, however, is more plausible than a formatting error, he said, because Supplemental tables 1 and 2 correspond exactly to the Duke 1 to Duke 7 sequence, suggesting the tables are correct and that the error might have occurred downstream, including in the manuscript.
The numbers should be consistent across all the ISCHEMIA manuscripts, Dr. Bakaeen added, but currently “don’t add up,” even after adjustment for different denominators, and especially for participants with left main disease.
They hope that publication of their letter, he said, will convince the authors to publicly share the data for patients in each of the seven modified Duke categories.
Lead author of the ISCHEMIA substudy, Harmony Reynolds, MD, New York (N.Y.) University Langone Health, told this news organization via email that as a result of a “formatting error in the transfer of data from the statistical output file to a Word document, data in Supplemental tables 1 and 2 were incorrect.”
She explained that they planned to present six, not seven, rows for the Duke score in the tables, collapsing the first two categories of nonobstructive disease (Duke 1-2), as they were in all other tables and figures. However, the Supplemental tables had incorrect row headings and because the Word program is designed to fill all available rows, it inserted the data from the output file into a seven-row table shell, duplicating the values for row 1 in the last row for left main disease of at least 50%.
“The data were correctly presented in the main manuscript tables and figures and in the remainder of the supplement, with a total of 659 patients in the subset with modified Duke prognostic index category 6 on coronary CT angiography,” Dr. Reynolds said.
She noted that Circulation will issue a correction. In addition, “we are in the process of preparing the data for public sharing soon. The data will include the Duke prognostic score at all levels.”
Circulation editor-in-chief Joseph A. Hill, MD, PhD, chief of cardiology at UT Southwestern Medical Center, Dallas, declined to be interviewed but confirmed via email that Dr. Bakaeen and Dr. Sabik’s letter and the correction will be published the week of May 16.
As for the delay, he said, “I received their reach-out just over 1 week ago, and per protocol, we conducted an internal evaluation of their allegations, which took a bit of time.”
A version of this article first appeared on Medscape.com.
A recent ISCHEMIA trial substudy is under scrutiny from surgeons for a data discrepancy, rekindling concerns about reliance on the landmark trial data in the latest coronary revascularization guidelines.
As previously reported, the main ISCHEMIA findings showed no significant benefit for an initial strategy of percutaneous coronary intervention (PCI) or coronary bypass graft surgery (CABG) over medical therapy in patients with stable moderate to severe ischemic heart disease.
The 2021 substudy by Reynolds et al. showed that coronary artery disease (CAD) severity, classified using the modified Duke Prognostic Index score, predicted 4-year mortality and myocardial infarction in the trial, whereas ischemia severity did not.
Cardiac surgeons Joseph F. Sabik III, MD, and Faisal Bakaeen, MD, however, spotted that only 40 patients are in the Duke category 6 group (three-vessel severe stenosis of at least 70% or two-vessel severe stenosis with a proximal left anterior descending lesion) in Supplemental tables 1 and 2, whereas 659 are in the main paper.
In addition, the Supplemental tables list the following:
- 659 patients in Duke group 5, not 894 as in the paper.
- 894 patients in Duke group 4, not 743 as in the paper.
- 743 patients in Duke group 3, not 179 as in the paper.
The surgeons penned a letter to Circulation early in April flagging the discrepancies, but say it was rejected April 15 because it was submitted outside the journal’s 6-week window for letters. They posted a public comment on the Remarq research platform, as advised by Circulation’s editorial office, and reached out directly to the authors and ISCHEMIA leadership.
“They just keep saying it’s a simple formatting error. Well, if it is a simple formatting error, then fix it,” Dr. Sabik, chair of surgery at University Hospitals Cleveland Medical Center, said in an interview. “But here we are now, a month later, and they still haven’t published our letter. Why? We’re the ones who identified the problem.”
Dr. Sabik said the accuracy of the data has important implications because the recent AHA/ACC/SCAI coronary revascularization guidelines used the ISCHEMIA data to downgrade the CABG recommendation for complex multivessel disease from class 1 to class 2B. Patients with a Duke 6 score are also typically the ones referred for CABG by today’s heart teams.
Several surgical societies have contested the guidelines, questioning whether the ISCHEMIA patients are truly reflective of those seen in clinical practice and questioning the decision to treat PCI and surgery as equivalent strategies to decrease ischemic events.
Dr. Bakaeen, from the Cleveland Clinic, told this news organization they don’t want a public battle over the data like the one that befell the EXCEL trial, and that it’s entirely possible the investigators might have inadvertently upgraded all the Duke score assignments by 1.
A systematic error, however, is more plausible than a formatting error, he said, because Supplemental tables 1 and 2 correspond exactly to the Duke 1 to Duke 7 sequence, suggesting the tables are correct and that the error might have occurred downstream, including in the manuscript.
The numbers should be consistent across all the ISCHEMIA manuscripts, Dr. Bakaeen added, but currently “don’t add up,” even after adjustment for different denominators, and especially for participants with left main disease.
They hope that publication of their letter, he said, will convince the authors to publicly share the data for patients in each of the seven modified Duke categories.
Lead author of the ISCHEMIA substudy, Harmony Reynolds, MD, New York (N.Y.) University Langone Health, told this news organization via email that as a result of a “formatting error in the transfer of data from the statistical output file to a Word document, data in Supplemental tables 1 and 2 were incorrect.”
She explained that they planned to present six, not seven, rows for the Duke score in the tables, collapsing the first two categories of nonobstructive disease (Duke 1-2), as they were in all other tables and figures. However, the Supplemental tables had incorrect row headings and because the Word program is designed to fill all available rows, it inserted the data from the output file into a seven-row table shell, duplicating the values for row 1 in the last row for left main disease of at least 50%.
“The data were correctly presented in the main manuscript tables and figures and in the remainder of the supplement, with a total of 659 patients in the subset with modified Duke prognostic index category 6 on coronary CT angiography,” Dr. Reynolds said.
She noted that Circulation will issue a correction. In addition, “we are in the process of preparing the data for public sharing soon. The data will include the Duke prognostic score at all levels.”
Circulation editor-in-chief Joseph A. Hill, MD, PhD, chief of cardiology at UT Southwestern Medical Center, Dallas, declined to be interviewed but confirmed via email that Dr. Bakaeen and Dr. Sabik’s letter and the correction will be published the week of May 16.
As for the delay, he said, “I received their reach-out just over 1 week ago, and per protocol, we conducted an internal evaluation of their allegations, which took a bit of time.”
A version of this article first appeared on Medscape.com.
FDA authorizes Pfizer’s COVID booster for kids ages 5 to 11
emergency use authorization (EUA), allowing the Pfizer-BioNTech COVID-19 booster shot for children ages 5 to 11 who are at least 5 months out from their first vaccine series.
According to the most recent data from the Centers for Disease Control and Prevention, 28.6% of children in this age group have received both initial doses of Pfizer’s COVID-19 vaccine, and 35.3% have received their first dose.
Pfizer’s vaccine trial involving 4,500 children showed few side effects among children younger than 12 who received a booster, or third dose, according to a company statement.
Pfizer asked the FDA for an amended authorization in April, after submitting data showing that a third dose in children between 5 and 11 raised antibodies targeting the Omicron variant by 36 times.
“While it has largely been the case that COVID-19 tends to be less severe in children than adults, the omicron wave has seen more kids getting sick with the disease and being hospitalized, and children may also experience longer-term effects, even following initially mild disease,” FDA Commissioner Robert M. Califf, MD, said in a news release.
A study done by the New York State Department of Health showed the effectiveness of Pfizer’s two-dose vaccine series fell from 68% to 12% 4-5 months after the second dose was given to children 5 to 11 during the Omicron surge. A CDC study published in March also showed that the Pfizer shot reduced the risk of Omicron by 31% in children 5 to 11, a significantly lower rate than for kids 12 to 15, who had a 59% risk reduction after receiving two doses.
To some experts, this data suggest an even greater need for children under 12 to be eligible for a third dose.
“Since authorizing the vaccine for children down to 5 years of age in October 2021, emerging data suggest that vaccine effectiveness against COVID-19 wanes after the second dose of the vaccine in all authorized populations,” says Peter Marks, MD, PhD, the director of the FDA’s Center for Biologics Evaluation and Research.
The CDC still needs to sign off on the shots before they can be allowed. The agency’s Advisory Committee on Immunization Practices is set to meet on May 19 to discuss boosters in this age group.
FDA advisory panels plan to meet next month to discuss allowing Pfizer’s and Moderna’s COVID-19 vaccines for children under 6 years old.
A version of this article first appeared on WebMD.com.
emergency use authorization (EUA), allowing the Pfizer-BioNTech COVID-19 booster shot for children ages 5 to 11 who are at least 5 months out from their first vaccine series.
According to the most recent data from the Centers for Disease Control and Prevention, 28.6% of children in this age group have received both initial doses of Pfizer’s COVID-19 vaccine, and 35.3% have received their first dose.
Pfizer’s vaccine trial involving 4,500 children showed few side effects among children younger than 12 who received a booster, or third dose, according to a company statement.
Pfizer asked the FDA for an amended authorization in April, after submitting data showing that a third dose in children between 5 and 11 raised antibodies targeting the Omicron variant by 36 times.
“While it has largely been the case that COVID-19 tends to be less severe in children than adults, the omicron wave has seen more kids getting sick with the disease and being hospitalized, and children may also experience longer-term effects, even following initially mild disease,” FDA Commissioner Robert M. Califf, MD, said in a news release.
A study done by the New York State Department of Health showed the effectiveness of Pfizer’s two-dose vaccine series fell from 68% to 12% 4-5 months after the second dose was given to children 5 to 11 during the Omicron surge. A CDC study published in March also showed that the Pfizer shot reduced the risk of Omicron by 31% in children 5 to 11, a significantly lower rate than for kids 12 to 15, who had a 59% risk reduction after receiving two doses.
To some experts, this data suggest an even greater need for children under 12 to be eligible for a third dose.
“Since authorizing the vaccine for children down to 5 years of age in October 2021, emerging data suggest that vaccine effectiveness against COVID-19 wanes after the second dose of the vaccine in all authorized populations,” says Peter Marks, MD, PhD, the director of the FDA’s Center for Biologics Evaluation and Research.
The CDC still needs to sign off on the shots before they can be allowed. The agency’s Advisory Committee on Immunization Practices is set to meet on May 19 to discuss boosters in this age group.
FDA advisory panels plan to meet next month to discuss allowing Pfizer’s and Moderna’s COVID-19 vaccines for children under 6 years old.
A version of this article first appeared on WebMD.com.
emergency use authorization (EUA), allowing the Pfizer-BioNTech COVID-19 booster shot for children ages 5 to 11 who are at least 5 months out from their first vaccine series.
According to the most recent data from the Centers for Disease Control and Prevention, 28.6% of children in this age group have received both initial doses of Pfizer’s COVID-19 vaccine, and 35.3% have received their first dose.
Pfizer’s vaccine trial involving 4,500 children showed few side effects among children younger than 12 who received a booster, or third dose, according to a company statement.
Pfizer asked the FDA for an amended authorization in April, after submitting data showing that a third dose in children between 5 and 11 raised antibodies targeting the Omicron variant by 36 times.
“While it has largely been the case that COVID-19 tends to be less severe in children than adults, the omicron wave has seen more kids getting sick with the disease and being hospitalized, and children may also experience longer-term effects, even following initially mild disease,” FDA Commissioner Robert M. Califf, MD, said in a news release.
A study done by the New York State Department of Health showed the effectiveness of Pfizer’s two-dose vaccine series fell from 68% to 12% 4-5 months after the second dose was given to children 5 to 11 during the Omicron surge. A CDC study published in March also showed that the Pfizer shot reduced the risk of Omicron by 31% in children 5 to 11, a significantly lower rate than for kids 12 to 15, who had a 59% risk reduction after receiving two doses.
To some experts, this data suggest an even greater need for children under 12 to be eligible for a third dose.
“Since authorizing the vaccine for children down to 5 years of age in October 2021, emerging data suggest that vaccine effectiveness against COVID-19 wanes after the second dose of the vaccine in all authorized populations,” says Peter Marks, MD, PhD, the director of the FDA’s Center for Biologics Evaluation and Research.
The CDC still needs to sign off on the shots before they can be allowed. The agency’s Advisory Committee on Immunization Practices is set to meet on May 19 to discuss boosters in this age group.
FDA advisory panels plan to meet next month to discuss allowing Pfizer’s and Moderna’s COVID-19 vaccines for children under 6 years old.
A version of this article first appeared on WebMD.com.
Why do clinical trials still underrepresent minority groups?
It’s no secret that, for decades, the participants in clinical trials for new drugs and medical devices haven’t accurately represented the diverse groups of patients the drugs and devices were designed for.
In a recently published draft guidance, the Food and Drug Administration recommended that companies in charge of running these trials should submit a proposal to the agency that would address how they plan to enroll more “clinically relevant populations” and historically underrepresented racial and ethnic groups.
It’s an issue that the U.S. has been trying to fix for years. In 1993, the NIH Revitalization Act was passed into law. It mandated the appropriate inclusion of women and racial minorities in all National Institutes of Health–funded research.
Since then, the FDA has put out plans that encourage trial sponsors to recruit more diverse enrollees, offering strategies and best practices rather than establishing requirements or quotas that companies would be forced to meet. Despite its efforts to encourage inclusion, people of color continue to be largely underrepresented in clinical trials.
Experts aren’t just calling for trial cohorts to reflect U.S. census data. Rather, the demographics of participants should match those of the diagnosis being studied. An analysis of 24 clinical trials of cardiovascular drugs, for example, found that Black Americans made up 2.9% of trial participants, compared with 83.1% for White people. Given that cardiovascular diseases affect Black Americans at almost the same rate as Whites (23.5% and 23.7%, respectively) – and keeping in mind that Black Americans make up 13.4% of the population and White people represent 76.3% – the degree of underrepresentation is glaring.
One commonly cited reason for this lack of representation is that people of color, especially Black Americans, have lingering feelings of mistrust toward the medical field. The U.S.-run Tuskegee study – during which researchers documented the natural progression of syphilis in hundreds of Black men who were kept from life-saving treatment – is, justifiably, often named as a notable source of that suspicion.
But blaming the disproportionately low numbers of Black participants in clinical trials on medical mistrust is an easy answer to a much more complicated issue, said cardiologist Clyde Yancy, MD, who also serves as the vice dean for diversity and inclusion at Northwestern University’s Feinberg School of Medicine, Chicago.
“We need to not put the onus on the back of the patient cohort, and say they are the problem,” Dr. Yancy said, adding that many trials add financial barriers and don’t provide proper transportation for participants who may live farther away.
The diversity of the study team itself – the institutions, researchers, and recruiters – also contributes to a lack of diversity in the participant pool. When considering all of these factors, “you begin to understand the complexity and the multidimensionality of why we have underrepresentation,” said Dr. Yancy. “So I would not promulgate the notion that this is simply because patients don’t trust the system.”
Soumya Niranjan, PhD, worked as a study coordinator at the Tulane Cancer Center in New Orleans, La., where she recruited patients for a prostate cancer study. After researching the impact of clinicians’ biases on the recruitment of racial and ethnic minorities in oncology trials, she found that some recruiters view patients of color as less promising participants.
“Who ends up being approached for a clinical trial is based on a preset rubric that one has in mind about a patient who may be eligible for a cancer study,” said Dr. Niranjan. “There is a characterization of, ‘we want to make sure this patient is compliant, that they will be a good historian and seem responsible.’ ... Our study showed that it kind of fell along racial lines.”
In her study, published in the journal Cancer in 2020, Dr. Niranjan wrote that researchers sometimes “perceived racial minority groups to have low knowledge of cancer clinical trials. This was considered to be a hindrance while explaining cancer clinical trials in the face of limited provider time during a clinical encounter.”
Some researchers believed minority participants, especially Black women, would be less likely to file study protocols. Others said people of color are more likely to be selfish.
She quoted one research investigator as saying Black people are less knowledgeable.
“African Americans I think have less knowledge,” the unnamed researcher said. “We take a little bit more time to explain to African American [sic]. I think ... they have more questions because we know they are not more knowledgeable so I think it takes time. They have a lot of questions.”
Progress over the years
The FDA’s recent draft builds upon a guidance from 2016, which already recommended that trial teams submit an inclusion plan to the agency at the earliest phase of development. While the recent announcement is another step in the right direction, it may not be substantial enough.
“There’s always an enrollment plan,” Dr. Niranjan said. “But those enrollment plans are not enforced. So if it’s not enforced, what does that look like?”
In an emailed statement to this news organization, Lola Fashoyin-Aje, MD, the deputy director of the FDA Oncology Center of Excellence’s division to expand diversity, emphasized that the draft guidance does not require anything, but that the agency “expect[s] sponsors will follow FDA’s recommendations as described in the draft guidance.”
Without requirements, it’s up to the sponsor to make the effort to enroll people with varied racial and ethnic backgrounds. During the development of the COVID-19 vaccine, Moderna announced that the company would slow the trial’s enrollment to ensure minority groups were properly represented.
Not every sponsor is as motivated to make this a concerted effort, and some simply don’t have the funds to allocate to strengthening the enrollment process.
“There’s so much red tape and paperwork to get the funding for a clinical trial,” said Julie Silver, MD, professor of physical medicine and rehabilitation at Harvard Medical School, Boston, who studies workforce diversity and inclusion. “Even when people are equitably included, the amount of funding they have to do the trial might not be enough to do an analysis that shows potential differences.”
Whether the FDA will enforce enrollment plans in the future remains an open question; however, Dr. Yancy said the most effective way to do this would be through incentives, rather than penalties.
According to Dr. Fashoyin-Aje, the FDA and sponsors “will learn from these submissions and over time, whether and how these diversity plans lead to meaningful changes in clinical trial representation will need to be assessed, including whether additional steps need to be taken.”
A version of this article first appeared on Medscape.com.
It’s no secret that, for decades, the participants in clinical trials for new drugs and medical devices haven’t accurately represented the diverse groups of patients the drugs and devices were designed for.
In a recently published draft guidance, the Food and Drug Administration recommended that companies in charge of running these trials should submit a proposal to the agency that would address how they plan to enroll more “clinically relevant populations” and historically underrepresented racial and ethnic groups.
It’s an issue that the U.S. has been trying to fix for years. In 1993, the NIH Revitalization Act was passed into law. It mandated the appropriate inclusion of women and racial minorities in all National Institutes of Health–funded research.
Since then, the FDA has put out plans that encourage trial sponsors to recruit more diverse enrollees, offering strategies and best practices rather than establishing requirements or quotas that companies would be forced to meet. Despite its efforts to encourage inclusion, people of color continue to be largely underrepresented in clinical trials.
Experts aren’t just calling for trial cohorts to reflect U.S. census data. Rather, the demographics of participants should match those of the diagnosis being studied. An analysis of 24 clinical trials of cardiovascular drugs, for example, found that Black Americans made up 2.9% of trial participants, compared with 83.1% for White people. Given that cardiovascular diseases affect Black Americans at almost the same rate as Whites (23.5% and 23.7%, respectively) – and keeping in mind that Black Americans make up 13.4% of the population and White people represent 76.3% – the degree of underrepresentation is glaring.
One commonly cited reason for this lack of representation is that people of color, especially Black Americans, have lingering feelings of mistrust toward the medical field. The U.S.-run Tuskegee study – during which researchers documented the natural progression of syphilis in hundreds of Black men who were kept from life-saving treatment – is, justifiably, often named as a notable source of that suspicion.
But blaming the disproportionately low numbers of Black participants in clinical trials on medical mistrust is an easy answer to a much more complicated issue, said cardiologist Clyde Yancy, MD, who also serves as the vice dean for diversity and inclusion at Northwestern University’s Feinberg School of Medicine, Chicago.
“We need to not put the onus on the back of the patient cohort, and say they are the problem,” Dr. Yancy said, adding that many trials add financial barriers and don’t provide proper transportation for participants who may live farther away.
The diversity of the study team itself – the institutions, researchers, and recruiters – also contributes to a lack of diversity in the participant pool. When considering all of these factors, “you begin to understand the complexity and the multidimensionality of why we have underrepresentation,” said Dr. Yancy. “So I would not promulgate the notion that this is simply because patients don’t trust the system.”
Soumya Niranjan, PhD, worked as a study coordinator at the Tulane Cancer Center in New Orleans, La., where she recruited patients for a prostate cancer study. After researching the impact of clinicians’ biases on the recruitment of racial and ethnic minorities in oncology trials, she found that some recruiters view patients of color as less promising participants.
“Who ends up being approached for a clinical trial is based on a preset rubric that one has in mind about a patient who may be eligible for a cancer study,” said Dr. Niranjan. “There is a characterization of, ‘we want to make sure this patient is compliant, that they will be a good historian and seem responsible.’ ... Our study showed that it kind of fell along racial lines.”
In her study, published in the journal Cancer in 2020, Dr. Niranjan wrote that researchers sometimes “perceived racial minority groups to have low knowledge of cancer clinical trials. This was considered to be a hindrance while explaining cancer clinical trials in the face of limited provider time during a clinical encounter.”
Some researchers believed minority participants, especially Black women, would be less likely to file study protocols. Others said people of color are more likely to be selfish.
She quoted one research investigator as saying Black people are less knowledgeable.
“African Americans I think have less knowledge,” the unnamed researcher said. “We take a little bit more time to explain to African American [sic]. I think ... they have more questions because we know they are not more knowledgeable so I think it takes time. They have a lot of questions.”
Progress over the years
The FDA’s recent draft builds upon a guidance from 2016, which already recommended that trial teams submit an inclusion plan to the agency at the earliest phase of development. While the recent announcement is another step in the right direction, it may not be substantial enough.
“There’s always an enrollment plan,” Dr. Niranjan said. “But those enrollment plans are not enforced. So if it’s not enforced, what does that look like?”
In an emailed statement to this news organization, Lola Fashoyin-Aje, MD, the deputy director of the FDA Oncology Center of Excellence’s division to expand diversity, emphasized that the draft guidance does not require anything, but that the agency “expect[s] sponsors will follow FDA’s recommendations as described in the draft guidance.”
Without requirements, it’s up to the sponsor to make the effort to enroll people with varied racial and ethnic backgrounds. During the development of the COVID-19 vaccine, Moderna announced that the company would slow the trial’s enrollment to ensure minority groups were properly represented.
Not every sponsor is as motivated to make this a concerted effort, and some simply don’t have the funds to allocate to strengthening the enrollment process.
“There’s so much red tape and paperwork to get the funding for a clinical trial,” said Julie Silver, MD, professor of physical medicine and rehabilitation at Harvard Medical School, Boston, who studies workforce diversity and inclusion. “Even when people are equitably included, the amount of funding they have to do the trial might not be enough to do an analysis that shows potential differences.”
Whether the FDA will enforce enrollment plans in the future remains an open question; however, Dr. Yancy said the most effective way to do this would be through incentives, rather than penalties.
According to Dr. Fashoyin-Aje, the FDA and sponsors “will learn from these submissions and over time, whether and how these diversity plans lead to meaningful changes in clinical trial representation will need to be assessed, including whether additional steps need to be taken.”
A version of this article first appeared on Medscape.com.
It’s no secret that, for decades, the participants in clinical trials for new drugs and medical devices haven’t accurately represented the diverse groups of patients the drugs and devices were designed for.
In a recently published draft guidance, the Food and Drug Administration recommended that companies in charge of running these trials should submit a proposal to the agency that would address how they plan to enroll more “clinically relevant populations” and historically underrepresented racial and ethnic groups.
It’s an issue that the U.S. has been trying to fix for years. In 1993, the NIH Revitalization Act was passed into law. It mandated the appropriate inclusion of women and racial minorities in all National Institutes of Health–funded research.
Since then, the FDA has put out plans that encourage trial sponsors to recruit more diverse enrollees, offering strategies and best practices rather than establishing requirements or quotas that companies would be forced to meet. Despite its efforts to encourage inclusion, people of color continue to be largely underrepresented in clinical trials.
Experts aren’t just calling for trial cohorts to reflect U.S. census data. Rather, the demographics of participants should match those of the diagnosis being studied. An analysis of 24 clinical trials of cardiovascular drugs, for example, found that Black Americans made up 2.9% of trial participants, compared with 83.1% for White people. Given that cardiovascular diseases affect Black Americans at almost the same rate as Whites (23.5% and 23.7%, respectively) – and keeping in mind that Black Americans make up 13.4% of the population and White people represent 76.3% – the degree of underrepresentation is glaring.
One commonly cited reason for this lack of representation is that people of color, especially Black Americans, have lingering feelings of mistrust toward the medical field. The U.S.-run Tuskegee study – during which researchers documented the natural progression of syphilis in hundreds of Black men who were kept from life-saving treatment – is, justifiably, often named as a notable source of that suspicion.
But blaming the disproportionately low numbers of Black participants in clinical trials on medical mistrust is an easy answer to a much more complicated issue, said cardiologist Clyde Yancy, MD, who also serves as the vice dean for diversity and inclusion at Northwestern University’s Feinberg School of Medicine, Chicago.
“We need to not put the onus on the back of the patient cohort, and say they are the problem,” Dr. Yancy said, adding that many trials add financial barriers and don’t provide proper transportation for participants who may live farther away.
The diversity of the study team itself – the institutions, researchers, and recruiters – also contributes to a lack of diversity in the participant pool. When considering all of these factors, “you begin to understand the complexity and the multidimensionality of why we have underrepresentation,” said Dr. Yancy. “So I would not promulgate the notion that this is simply because patients don’t trust the system.”
Soumya Niranjan, PhD, worked as a study coordinator at the Tulane Cancer Center in New Orleans, La., where she recruited patients for a prostate cancer study. After researching the impact of clinicians’ biases on the recruitment of racial and ethnic minorities in oncology trials, she found that some recruiters view patients of color as less promising participants.
“Who ends up being approached for a clinical trial is based on a preset rubric that one has in mind about a patient who may be eligible for a cancer study,” said Dr. Niranjan. “There is a characterization of, ‘we want to make sure this patient is compliant, that they will be a good historian and seem responsible.’ ... Our study showed that it kind of fell along racial lines.”
In her study, published in the journal Cancer in 2020, Dr. Niranjan wrote that researchers sometimes “perceived racial minority groups to have low knowledge of cancer clinical trials. This was considered to be a hindrance while explaining cancer clinical trials in the face of limited provider time during a clinical encounter.”
Some researchers believed minority participants, especially Black women, would be less likely to file study protocols. Others said people of color are more likely to be selfish.
She quoted one research investigator as saying Black people are less knowledgeable.
“African Americans I think have less knowledge,” the unnamed researcher said. “We take a little bit more time to explain to African American [sic]. I think ... they have more questions because we know they are not more knowledgeable so I think it takes time. They have a lot of questions.”
Progress over the years
The FDA’s recent draft builds upon a guidance from 2016, which already recommended that trial teams submit an inclusion plan to the agency at the earliest phase of development. While the recent announcement is another step in the right direction, it may not be substantial enough.
“There’s always an enrollment plan,” Dr. Niranjan said. “But those enrollment plans are not enforced. So if it’s not enforced, what does that look like?”
In an emailed statement to this news organization, Lola Fashoyin-Aje, MD, the deputy director of the FDA Oncology Center of Excellence’s division to expand diversity, emphasized that the draft guidance does not require anything, but that the agency “expect[s] sponsors will follow FDA’s recommendations as described in the draft guidance.”
Without requirements, it’s up to the sponsor to make the effort to enroll people with varied racial and ethnic backgrounds. During the development of the COVID-19 vaccine, Moderna announced that the company would slow the trial’s enrollment to ensure minority groups were properly represented.
Not every sponsor is as motivated to make this a concerted effort, and some simply don’t have the funds to allocate to strengthening the enrollment process.
“There’s so much red tape and paperwork to get the funding for a clinical trial,” said Julie Silver, MD, professor of physical medicine and rehabilitation at Harvard Medical School, Boston, who studies workforce diversity and inclusion. “Even when people are equitably included, the amount of funding they have to do the trial might not be enough to do an analysis that shows potential differences.”
Whether the FDA will enforce enrollment plans in the future remains an open question; however, Dr. Yancy said the most effective way to do this would be through incentives, rather than penalties.
According to Dr. Fashoyin-Aje, the FDA and sponsors “will learn from these submissions and over time, whether and how these diversity plans lead to meaningful changes in clinical trial representation will need to be assessed, including whether additional steps need to be taken.”
A version of this article first appeared on Medscape.com.